脊索细胞与椎间盘退变的相关性研究
|
摘要
第一部分:兔腰椎间盘退变模型建立
目的:纤维环损伤诱导椎间盘退变建立实验动物模型。
方法:新西兰大白兔12只年龄2岁左右,体重2.0-3.5KG左右,雌雄不限。2只作为正常对照未行手术,其余10只进行手术制造椎间盘退变模型。
手术采用10%水合氯醛3ml/kg耳缘静脉注射麻醉、备皮、碘伏消毒、铺巾。采用腰椎背侧纵切口,椎旁肌腹侧2cm,从胸廓下缘2cm至骨盆环,脊柱L1-L6左前外侧被暴露,钝性分离椎前软组织,骨盆环作为L5/6间隙的标志。用18G针头分别在L2/3、L4/5椎间盘进行穿刺,L3/4和L5/6作为自身对照。术后2、4、8、16、32周各随机选取2只兔,行脊柱MRI检查并行免疫组化及组织学观察。
结果:术后第3～10周造模后的椎间盘MRI T2WI信号呈现持续减弱趋势,而内对照非手术节段髓核信号强度在观察期内无明显变化。各组椎间盘分级分值的变化显示,从术后2周开始,穿刺椎间隙与自身内对照椎间隙比较差异均有统计学意义(P < 0.05);穿刺髓核MRI T2相信号呈进行性下降,至术后16周呈快速下降。免疫组化及组织学观察发现髓核细胞的数量及Ⅱ型胶原含量较对照间盘进行性减少(P<0.01)。
结论:纤维环穿刺诱导兔椎间盘退变的动物模型能再现IDD发展的客观规律而且模型制作简单、重复性好。
第二部分:不同年龄组兔椎间盘细胞分布类型研究
目的:分析脊索细胞和软骨样细胞细胞形态及随年龄增长时的分布情况
方法:取3月龄组和3年龄组新西兰大白兔各5只,完整取出腰椎脊柱,兔腰椎椎间盘纤维环横行切开,完整取出髓核,放入petri培养皿,PPS洗液调制PH7.21%低熔点的琼脂糖覆盖,覆盖、固定组织,然后植入10%的中性福尔马林中固定,对于髓核和纤维环边缘不清的三度退变椎间盘,用6mm直径的穿刺针取出椎间盘中央部分,琼脂糖包埋的髓核。荧光抗淬灭封片剂封片,激光共聚焦显微镜下测量细胞大小以及CD44和vimentin在脊索细胞和软骨样髓核细胞内表达的平均荧光强度。
结果:应用共聚焦显微镜,可以在新西兰大白兔椎间盘髓核标本中,发现两种细胞:脊索细胞和软骨细胞。两种细胞在大小上有明显的区别,在3月龄新西兰大白兔的椎间盘中,脊索细胞占主要部分。从细胞计数上分析,脊索细胞占全部的80.92%,与软骨样髓核细胞数量有着明显的差异;在3年组新西兰大白兔的椎间盘中,软骨样髓核细胞占主要部分,而脊索细胞数量较3月组明显减少,比例为32.8%,表明脊索细胞数量随年龄的增长而递减,软骨样髓核细胞的数量随年龄递增。Vimentin和CD44平均荧光强度在脊索细胞内明显高于软骨样髓核细胞,两者相比有显著统计学意义。
结论:脊索细胞内这两种蛋白的表达强度显著高于软骨样髓核细胞(P<0.01)且与年龄呈负相关,年龄越小,表达越强。提示随着脊索细胞成熟和老化,与脊索细胞调控和发挥功能相关的蛋白表达量逐渐下降。其对周围环境发挥作用亦逐渐减少。
第三部分:脊索细胞在兔椎间盘退变过程中的作用和转归
目的:对脊索细胞在椎间盘退变过程中的作用的研究
方法:新西兰大白兔28只,分3月龄和3年龄两组,每组共14只,3月龄组体重1.5±2.0kg,3年龄组体重3.0-4.5kg左右,雌雄不限。每组中有2只作为正常对照未行手术。每组其余12只进入手术制造椎间盘退变模型。术后2,4,8,16,24周行MRI影像学确认椎间盘退变后,经耳缘静脉注入空气10 mL处死实验动物,获取手术节段和正常自身对照的椎间盘髓核组织,手术节段髓核作为退变组,自身未作处理间隙作为对照组。取下的髓核组织分成两部分,一部分行免疫组织切片后进行HE染色与aggrecan,Ⅱ型胶原和PCNA染色,免疫组织化学染色观察。另一部分-70度保存,RT-PCR检测。
结果:椎间盘退变模型显示脊索细胞逐渐消失,被软骨样髓核细胞和不规则的基质取代,3月组兔椎间盘退变模型,前16周脊索细胞PCNA阳性细胞表达率基本保持稳定,16周后显著减少,软骨样髓核细胞的PCNA阳性细胞表达率16周后逐渐增多。3年组脊索细胞PCNA阳性细胞表达率前8周逐渐增高,后逐渐下降;软骨样髓核细胞PCNA阳性表达细胞率前4周基本保持稳定,8周后逐渐增高。
结论:实验两个年龄组在出现蛋白多糖和Ⅱ型胶原RT-PCR水平下降,MRI T2像信号出现明显降低后,术后相同时间点3月龄组组织学观测较3年组存在较多的脊索细胞,虽然该细胞在PCNA和aggrecan蛋白水平表达两组无显著差异,但髓核细胞PCNA和aggrecan蛋白水平3月组却明显高于3年组。一定程度显示髓核细胞增殖和蛋白多糖分泌的能力与脊索细胞的数目有关。
Part I: rabbit lumbar intervertebral disc degeneration model building
Objectives: To establish a rabbit model of intervertebral disc degeneration induced by puncturing the anulus fibrosus with needles of defined gauges
Methods: The L2/3 and L4/5 (L3 / 4 and L5 / 6 as self-control) intervetebral discs of New Zealand white rabbit in ordinary grade were stabbed by 16-gauge transfixion pin into a depth of 5 mm in the anterolateral annulus fibrosus magnetic resonance imaging scans of the stabbed discs and intact discs were performed preoperatively and at the2th,4th,8th.16th and 32th week af ter surgery. The histologic and immunohistochemical analyses were performed after the animals were killed and the materials were ext racted.
Results: In the magnetic resonance imaging,the stabbed discs exhibited a progressive decrease of signal intensity in T2-weighted images which start at 2 week Statistically significant (P <0.05)after stabbing and last for 16 weeks.Immunohistochemical and histologic analyses revealed progressive decrease of chondrocyte-like cells and type II collagen (P<0.01).
Conclusions: The stabbing approach results in a slowly progressive intervertebral disc degeneration in rabbit model.This model is available for studying the status intervertebral disc degeneration.Although the rabbits of the spine in bio-mechanics and anatomy of human existence with some differences, but the disc tissue structure similar to humans, it can be used as animal models of IDD research, and may for this kind of research a large sample of experimental data.
Part II: different age groups of rabbit intervertebral disc cells in the distribution of types of research
Objectives: To evaluate notochordal cells and chondrocyte cell morphology and distribution with each stage of ages.
Methods: The experimental group to take 10 New Zealand white rabbits, weighing 2±0.5kg, 2 years old, complete, remove the lumbar spine, rampant rabbit lumbar intervertebral disc annulus incision, complete remove the nucleus, into the petri dish, PPS lotion modulation PH7. 21% of low melting point agarose coverage, coverage, fixed tissue, and then implanted in 10% neutral formalin fixed, for the edge of nucleus pulposus and annulus fibrosus unclear degenerative disc three times, with 6mm diameter needle out disc central part of the agarose-embedded nucleus. Fluorescence quenching of anti-sealing tablet Fengpian laser confocal microscope observation, semi-quantitative.
Results: Confocal microscopy can be in New Zealand white rabbit nucleus pulposus samples, we found two kinds of cells, notochord cells and chondrocytes in cell size between the two although there are obvious differences, but the 3-month-old when the intervertebral discs account for large-cell the main part, from the cell counts on the analysis of large cells accounted for all of the 80.92%, and the small cells have very different; in three years, when the sharp increase in the number of small cells, while the large number of cells is decreased, the proportion of 32.8% that large cell from 3 months to 3 years is to reduce the number, while a small number of cells increased faster. Vimentin immunofluorescence intensity of the average optical density of semi-quantitative analysis, and average optical density of CD44 immunofluorescence intensity of semi-quantitative analysis (P <0.01, P <0.05), there are statistically significant.
Conclusions: Select notochord cells in this experiment the characteristic marker CD44 and Vimentin fluorescent mark was measured in notochord cells and cartilage-like nucleus pulposus cells, the average fluorescence intensity, results showed that: notochord cells expression intensity of these two proteins was significantly higher than medullary nucleated cells (P<0.01), and negatively correlated with age, younger, stronger expression. Tip cell maturation and aging as the notochord, and notochord cells, regulation and function-related protein expression gradually decreased. To play a role in its surrounding environment is also reduced gradually.
Part III: notochord cells in the rabbit intervertebral disc degeneration in the process of the role and fate
Objectives: To evaluate the roles of notochord cells in the process of disc degeneration.
Methods: To take New Zealand white rabbits divided into 3-month-old and 3 years two groups of a total of 14, in March body weight 1.5±2.0kg, 3 year-old group of about 3.0-4.5kg body weight of 28. Each has two-line operation is not as normal controls. The remaining 12 rats in each group into the manufacture of disc degeneration model of operation. Lines at each time point imaging MRI confirmed disc degeneration, via ear vein injection of 10 mL of air experimental animals were sacrificed, access to surgery and the normal self-control segment of the intervertebral disc nucleus pulposus, surgical segmental degeneration of nucleus pulposus as a group, self - the absence of treatment gap for a control group. Remove the nucleus pulposus is divided into two parts, part of the line-free tissue sections stained with HE after aggrecan,Ⅱ-type collagen and PCNA staining, immunohistochemical staining. Another part of -70 degrees to save, RT-PCR detection.
Results: Intervertebral disc degeneration models show that notochordal cells gradually disappear, being irregular cartilage-like matrix of nucleus pulposus cells and replaced in March of rabbit disc degeneration model, before 16 weeks of notochord cells showed PCNA expression, 16 weeks after the spinal cord cells were significantly reduced, did not express PCNA, group cartilage-like cells PCNA16 weeks after an increase in cartilage-like nucleus pulposus cells, showing positive staining; March group notochord cells PCNA-positive cells gradually increased the rate of eight weeks before 16 weeks, decreased gradually. Cartilage-like nucleus pulposus cells, PCNA-positive cells 4 weeks before the rate remained stable, increased gradually after 8 weeks. Nucleus pulposus cells, PCNA and aggrecan protein levels in March group was significantly higher than 3-year group, notochord cells in the first 2 weeks of basic stability, the latter dropped significantly. Cartilage-like nucleus pulposus cells in the first 8 weeks of basic stability, the latter slightly increased.
Conclusions: The experimental two age groups in the event of proteoglycan and collagen typeⅡRT-PCR reduction in the level, MRI T2 signal and decreased significantly as the following time points after the same group in March compared with the histological observation of the 3-year group there are more notochord cells, Although the cellular protein level of PCNA and expression of aggrecan was no significant difference between the two groups, but the nucleus pulposus cells, PCNA and aggrecan protein levels in March group was significantly higher than 3-year group. Nucleus pulposus cells show a certain degree of proliferation and proteoglycan secretion capacity and the number of cells in the spinal cord.
目的:纤维环损伤诱导椎间盘退变建立实验动物模型。
方法:新西兰大白兔12只年龄2岁左右,体重2.0-3.5KG左右,雌雄不限。2只作为正常对照未行手术,其余10只进行手术制造椎间盘退变模型。
手术采用10%水合氯醛3ml/kg耳缘静脉注射麻醉、备皮、碘伏消毒、铺巾。采用腰椎背侧纵切口,椎旁肌腹侧2cm,从胸廓下缘2cm至骨盆环,脊柱L1-L6左前外侧被暴露,钝性分离椎前软组织,骨盆环作为L5/6间隙的标志。用18G针头分别在L2/3、L4/5椎间盘进行穿刺,L3/4和L5/6作为自身对照。术后2、4、8、16、32周各随机选取2只兔,行脊柱MRI检查并行免疫组化及组织学观察。
结果:术后第3～10周造模后的椎间盘MRI T2WI信号呈现持续减弱趋势,而内对照非手术节段髓核信号强度在观察期内无明显变化。各组椎间盘分级分值的变化显示,从术后2周开始,穿刺椎间隙与自身内对照椎间隙比较差异均有统计学意义(P < 0.05);穿刺髓核MRI T2相信号呈进行性下降,至术后16周呈快速下降。免疫组化及组织学观察发现髓核细胞的数量及Ⅱ型胶原含量较对照间盘进行性减少(P<0.01)。
结论:纤维环穿刺诱导兔椎间盘退变的动物模型能再现IDD发展的客观规律而且模型制作简单、重复性好。
第二部分:不同年龄组兔椎间盘细胞分布类型研究
目的:分析脊索细胞和软骨样细胞细胞形态及随年龄增长时的分布情况
方法:取3月龄组和3年龄组新西兰大白兔各5只,完整取出腰椎脊柱,兔腰椎椎间盘纤维环横行切开,完整取出髓核,放入petri培养皿,PPS洗液调制PH7.21%低熔点的琼脂糖覆盖,覆盖、固定组织,然后植入10%的中性福尔马林中固定,对于髓核和纤维环边缘不清的三度退变椎间盘,用6mm直径的穿刺针取出椎间盘中央部分,琼脂糖包埋的髓核。荧光抗淬灭封片剂封片,激光共聚焦显微镜下测量细胞大小以及CD44和vimentin在脊索细胞和软骨样髓核细胞内表达的平均荧光强度。
结果:应用共聚焦显微镜,可以在新西兰大白兔椎间盘髓核标本中,发现两种细胞:脊索细胞和软骨细胞。两种细胞在大小上有明显的区别,在3月龄新西兰大白兔的椎间盘中,脊索细胞占主要部分。从细胞计数上分析,脊索细胞占全部的80.92%,与软骨样髓核细胞数量有着明显的差异;在3年组新西兰大白兔的椎间盘中,软骨样髓核细胞占主要部分,而脊索细胞数量较3月组明显减少,比例为32.8%,表明脊索细胞数量随年龄的增长而递减,软骨样髓核细胞的数量随年龄递增。Vimentin和CD44平均荧光强度在脊索细胞内明显高于软骨样髓核细胞,两者相比有显著统计学意义。
结论:脊索细胞内这两种蛋白的表达强度显著高于软骨样髓核细胞(P<0.01)且与年龄呈负相关,年龄越小,表达越强。提示随着脊索细胞成熟和老化,与脊索细胞调控和发挥功能相关的蛋白表达量逐渐下降。其对周围环境发挥作用亦逐渐减少。
第三部分:脊索细胞在兔椎间盘退变过程中的作用和转归
目的:对脊索细胞在椎间盘退变过程中的作用的研究
方法:新西兰大白兔28只,分3月龄和3年龄两组,每组共14只,3月龄组体重1.5±2.0kg,3年龄组体重3.0-4.5kg左右,雌雄不限。每组中有2只作为正常对照未行手术。每组其余12只进入手术制造椎间盘退变模型。术后2,4,8,16,24周行MRI影像学确认椎间盘退变后,经耳缘静脉注入空气10 mL处死实验动物,获取手术节段和正常自身对照的椎间盘髓核组织,手术节段髓核作为退变组,自身未作处理间隙作为对照组。取下的髓核组织分成两部分,一部分行免疫组织切片后进行HE染色与aggrecan,Ⅱ型胶原和PCNA染色,免疫组织化学染色观察。另一部分-70度保存,RT-PCR检测。
结果:椎间盘退变模型显示脊索细胞逐渐消失,被软骨样髓核细胞和不规则的基质取代,3月组兔椎间盘退变模型,前16周脊索细胞PCNA阳性细胞表达率基本保持稳定,16周后显著减少,软骨样髓核细胞的PCNA阳性细胞表达率16周后逐渐增多。3年组脊索细胞PCNA阳性细胞表达率前8周逐渐增高,后逐渐下降;软骨样髓核细胞PCNA阳性表达细胞率前4周基本保持稳定,8周后逐渐增高。
结论:实验两个年龄组在出现蛋白多糖和Ⅱ型胶原RT-PCR水平下降,MRI T2像信号出现明显降低后,术后相同时间点3月龄组组织学观测较3年组存在较多的脊索细胞,虽然该细胞在PCNA和aggrecan蛋白水平表达两组无显著差异,但髓核细胞PCNA和aggrecan蛋白水平3月组却明显高于3年组。一定程度显示髓核细胞增殖和蛋白多糖分泌的能力与脊索细胞的数目有关。
Part I: rabbit lumbar intervertebral disc degeneration model building
Objectives: To establish a rabbit model of intervertebral disc degeneration induced by puncturing the anulus fibrosus with needles of defined gauges
Methods: The L2/3 and L4/5 (L3 / 4 and L5 / 6 as self-control) intervetebral discs of New Zealand white rabbit in ordinary grade were stabbed by 16-gauge transfixion pin into a depth of 5 mm in the anterolateral annulus fibrosus magnetic resonance imaging scans of the stabbed discs and intact discs were performed preoperatively and at the2th,4th,8th.16th and 32th week af ter surgery. The histologic and immunohistochemical analyses were performed after the animals were killed and the materials were ext racted.
Results: In the magnetic resonance imaging,the stabbed discs exhibited a progressive decrease of signal intensity in T2-weighted images which start at 2 week Statistically significant (P <0.05)after stabbing and last for 16 weeks.Immunohistochemical and histologic analyses revealed progressive decrease of chondrocyte-like cells and type II collagen (P<0.01).
Conclusions: The stabbing approach results in a slowly progressive intervertebral disc degeneration in rabbit model.This model is available for studying the status intervertebral disc degeneration.Although the rabbits of the spine in bio-mechanics and anatomy of human existence with some differences, but the disc tissue structure similar to humans, it can be used as animal models of IDD research, and may for this kind of research a large sample of experimental data.
Part II: different age groups of rabbit intervertebral disc cells in the distribution of types of research
Objectives: To evaluate notochordal cells and chondrocyte cell morphology and distribution with each stage of ages.
Methods: The experimental group to take 10 New Zealand white rabbits, weighing 2±0.5kg, 2 years old, complete, remove the lumbar spine, rampant rabbit lumbar intervertebral disc annulus incision, complete remove the nucleus, into the petri dish, PPS lotion modulation PH7. 21% of low melting point agarose coverage, coverage, fixed tissue, and then implanted in 10% neutral formalin fixed, for the edge of nucleus pulposus and annulus fibrosus unclear degenerative disc three times, with 6mm diameter needle out disc central part of the agarose-embedded nucleus. Fluorescence quenching of anti-sealing tablet Fengpian laser confocal microscope observation, semi-quantitative.
Results: Confocal microscopy can be in New Zealand white rabbit nucleus pulposus samples, we found two kinds of cells, notochord cells and chondrocytes in cell size between the two although there are obvious differences, but the 3-month-old when the intervertebral discs account for large-cell the main part, from the cell counts on the analysis of large cells accounted for all of the 80.92%, and the small cells have very different; in three years, when the sharp increase in the number of small cells, while the large number of cells is decreased, the proportion of 32.8% that large cell from 3 months to 3 years is to reduce the number, while a small number of cells increased faster. Vimentin immunofluorescence intensity of the average optical density of semi-quantitative analysis, and average optical density of CD44 immunofluorescence intensity of semi-quantitative analysis (P <0.01, P <0.05), there are statistically significant.
Conclusions: Select notochord cells in this experiment the characteristic marker CD44 and Vimentin fluorescent mark was measured in notochord cells and cartilage-like nucleus pulposus cells, the average fluorescence intensity, results showed that: notochord cells expression intensity of these two proteins was significantly higher than medullary nucleated cells (P<0.01), and negatively correlated with age, younger, stronger expression. Tip cell maturation and aging as the notochord, and notochord cells, regulation and function-related protein expression gradually decreased. To play a role in its surrounding environment is also reduced gradually.
Part III: notochord cells in the rabbit intervertebral disc degeneration in the process of the role and fate
Objectives: To evaluate the roles of notochord cells in the process of disc degeneration.
Methods: To take New Zealand white rabbits divided into 3-month-old and 3 years two groups of a total of 14, in March body weight 1.5±2.0kg, 3 year-old group of about 3.0-4.5kg body weight of 28. Each has two-line operation is not as normal controls. The remaining 12 rats in each group into the manufacture of disc degeneration model of operation. Lines at each time point imaging MRI confirmed disc degeneration, via ear vein injection of 10 mL of air experimental animals were sacrificed, access to surgery and the normal self-control segment of the intervertebral disc nucleus pulposus, surgical segmental degeneration of nucleus pulposus as a group, self - the absence of treatment gap for a control group. Remove the nucleus pulposus is divided into two parts, part of the line-free tissue sections stained with HE after aggrecan,Ⅱ-type collagen and PCNA staining, immunohistochemical staining. Another part of -70 degrees to save, RT-PCR detection.
Results: Intervertebral disc degeneration models show that notochordal cells gradually disappear, being irregular cartilage-like matrix of nucleus pulposus cells and replaced in March of rabbit disc degeneration model, before 16 weeks of notochord cells showed PCNA expression, 16 weeks after the spinal cord cells were significantly reduced, did not express PCNA, group cartilage-like cells PCNA16 weeks after an increase in cartilage-like nucleus pulposus cells, showing positive staining; March group notochord cells PCNA-positive cells gradually increased the rate of eight weeks before 16 weeks, decreased gradually. Cartilage-like nucleus pulposus cells, PCNA-positive cells 4 weeks before the rate remained stable, increased gradually after 8 weeks. Nucleus pulposus cells, PCNA and aggrecan protein levels in March group was significantly higher than 3-year group, notochord cells in the first 2 weeks of basic stability, the latter dropped significantly. Cartilage-like nucleus pulposus cells in the first 8 weeks of basic stability, the latter slightly increased.
Conclusions: The experimental two age groups in the event of proteoglycan and collagen typeⅡRT-PCR reduction in the level, MRI T2 signal and decreased significantly as the following time points after the same group in March compared with the histological observation of the 3-year group there are more notochord cells, Although the cellular protein level of PCNA and expression of aggrecan was no significant difference between the two groups, but the nucleus pulposus cells, PCNA and aggrecan protein levels in March group was significantly higher than 3-year group. Nucleus pulposus cells show a certain degree of proliferation and proteoglycan secretion capacity and the number of cells in the spinal cord.
引文
[1] Yang F, Leung VY, Luk KD, Chan D, Cheung KM. Mesenchymal stem cells arrest intervertebral disc degeneration through chondrocytic differentiation and stimulationof endogenous cells. Mol Ther. 2009. 17(11): 1959-66.
[2] Hunter CJ, Matyas JR, Duncan NA. The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering. Tissue Eng. 2003. 9(4): 667-77.
[3] Wasiak R, Pransky GS, Webster BS. Methodological challenges in studying recurrence of low back pain. J Occup Rehabil. 2003. 13(1): 21-31.
[4] Gilbertson L, Ahn SH, Teng PN, Studer RK, Niyibizi C, Kang JD. The effects of recombinant human bone morphogenetic protein-2, recombinant human bone morphogenetic protein-12, and adenoviral bone morphogenetic protein-12 on matrix synthesis in human annulus fibrosis and nucleus pulposus cells. Spine J. 2008. 8(3): 449-56.
[5] Hunter CJ, Matyas JR, Duncan NA. Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison. J Anat. 2004. 205(5): 357-62.
[6] Guehring T, Nerlich A, Kroeber M, Richter W, Omlor GW. Sensitivity of notochordal disc cells to mechanical loading: an experimental animal study. Eur Spine J. 2010. 19(1): 113-21.
[7] Mwale F, Wang HT, Petit A, et al. The effect of novel nitrogen-rich plasma polymer coatings on the phenotypic profile of notochordal cells. Biomed Eng Online. 2007. 6: 33.
[8] Erwin WM, Inman RD. Notochord cells regulate intervertebral disc chondrocyte proteoglycan production and cell proliferation. Spine (Phila Pa 1976). 2006. 31(10): 1094-9.
[9] Erwin WM. The Notochord, Notochordal cell and CTGF/CCN-2: ongoing activity from development through maturation. J Cell Commun Signal. 2008. 2(3-4): 59-65.
[10] Erwin WM, Ashman K, O'Donnel P, Inman RD. Nucleus pulposus notochord cells secrete connective tissue growth factor and up-regulate proteoglycan expression by intervertebral disc chondrocytes. Arthritis Rheum. 2006. 54(12): 3859-67.
[11] Rastogi A, Thakore P, Leung A, et al. Environmental regulation of notochordal geneexpression in nucleus pulposus cells. J Cell Physiol. 2009. 220(3): 698-705.
[12] Boyd LM, Chen J, Kraus VB, Setton LA. Conditioned medium differentially regulates matrix protein gene expression in cells of the intervertebral disc. Spine (Phila Pa 1976). 2004. 29(20): 2217-22.
[13] Masuda K, Imai Y, Okuma M, et al. Osteogenic protein-1 injection into a degenerated disc induces the restoration of disc height and structural changes in the rabbit anular puncture model. Spine (Phila Pa 1976). 2006. 31(7): 742-54.
[14] Horwitz, T. The human notochord: A study of its development and regression, variations, and pathologic derivative,chordoma. Indianapolis: 1977.
[15] Adler, J.H., Schoenbaum, M., and Silberberg, R. Early onset of disk degeneration and spondylosis in sand rats (Psammomys obesus). Vet. Pathol. 20, 13, 1983.
[16] Moskowitz, R.W., Ziv, I., Denko, C.W., Boja, B., Jones,P.K., and Adler, J.H.Spondylosis in sand rats: A model of intervertebral disc degeneration and hyperostosis. J. Orthop.Res. 8, 401, 1990.
[17] Hansen, H.J. A pathologic–anatomical study on disc degeneration in dog. Acta Orthop. Scand. Suppl. 11, 1952.
[18] Maldonado, B.A., and Oegema, T.R.J. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J. Orthop. Res. 10, 677, 1992.
[19] Scott, N.A., Harris, P.F., and Bagnall, K.M. A morphological and histological study of the postnatal development of intervertebral discs in the lumbar spine of the rabbit. J. Anat. 130, 75, 1980.
[20] Smith, J.W., and Serafini-Fracassini, A. The distribution of the proteinpolysaccharide complex in the nucleus pulposus matrix in young rabbits. J. Cell Sci. 3, 33, 1968.
[21] Kathmann, I., Cizinauskas, S., Rytz, U., Lang, J., and Jaggy, A. Spontaneous lumbar intervertebral disc protrusion in cats: Literature review and case presentations. J. Feline Med. Surg. 2, 207, 2000.
[22] Hansen, H.J. Comparative views on the pathology of disk degeneration in animals. Lab. Invest. 8, 1242, 1959.
[23] Butler, W.F. Comparative anatomy and development of the mammalian disc. In: Gosh, P., ed. The Biology of the Intervertebral Disc. Boca Raton, FL: CRC Press, 1989, pp.84–108.
[24]Carlier, E.W. The fate of the notochord and development of the intervertebral disc in the sheep. J. Anat. Phys. 24,573, 1890.
[1] Choi KS, Cohn MJ, Harfe BD. Identification of nucleus pulposus precursor cells and notochordal remnants in the mouse: implications for disk degeneration and chordoma formation. Dev Dyn. 2008. 237(12): 3953-8.
[2] Singh K, Masuda K, An HS. Animal models for human disc degeneration. Spine J. 2005. 5(6 Suppl): 267S-279S.
[3] Alini M, Eisenstein SM, Ito K, et al. Are animal models useful for studying human disc disorders/degeneration. Eur Spine J. 2008. 17(1): 2-19.
[4] Hunter CJ, Matyas JR, Duncan NA. Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison. J Anat. 2004. 205(5): 357-62.
[5] Kroeber MW, Unglaub F, Wang H, et al. New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration. Spine (Phila Pa 1976). 2002. 27(23): 2684-90.
[6] Sobajima S, Kompel JF, Kim JS, et al. A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology. Spine (Phila Pa 1976). 2005. 30(1): 15-24.
[7] Colloca CJ, Keller TS, Moore RJ, Harrison DE, Gunzburg R. Validation of a noninvasive dynamic spinal stiffness assessment methodology in an animal model of intervertebral disc degeneration. Spine (Phila Pa 1976). 2009. 34(18): 1900-5.
[8] Melrose J, Smith SM, Fuller ES, et al. Biglycan and fibromodulin fragmentation correlates with temporal and spatial annular remodelling in experimentally injured ovine intervertebral discs. Eur Spine J. 2007. 16(12): 2193-205.
[9] Melrose J, Ghosh P, Taylor TK, Latham J, Moore R. Topographical variation in the catabolism of aggrecan in an ovine annular lesion model of experimental disc degeneration. J Spinal Disord. 1997. 10(1): 55-67.
[10] Hoogendoorn RJ, Wuisman PI, Smit TH, Everts VE, Helder MN. Experimental intervertebral disc degeneration induced by chondroitinase ABC in the goat. Spine (Phila Pa 1976). 2007. 32(17): 1816-25.
[11]张闻力,刘浩,李坛珠.椎间盘退变动物模型的研究进展.中国修复重建外科杂志. 2007. 21(11): 1259-1262.
[12]屈开钛(综述),徐永清(审校),王非(审校).实验介导椎间盘退变动物模型的研究进展.昆明医学院学报.2008,29(B06).-219-223.昆明医学院学报.2008,29(B06).-219-223(昆明医学院学报.2008,29(B06).-219-223):昆明医学院学报.2008,29(B06).-219-223.
[13] Cassidy JD, Yong-Hing K, Kirkaldy-Willis WH, Wilkinson AA. A study of the effects of bipedism and upright posture on the lumbosacral spine and paravertebral muscles of the Wistar rat. Spine (Phila Pa 1976). 1988. 13(3): 301-8.
[14] Waters PM, Lipson SJ. Modification of the degenerative response in experimentalintervertebral disk herniation in rabbits. J Spinal Disord. 1988. 1(1): 81-5.
[15] Lipson SJ. Metaplastic proliferative fibrocartilage as an alternative concept to herniated intervertebral disc. Spine (Phila Pa 1976). 1988. 13(9): 1055-60.
[16] Sobajima S, Kompel JF, Kim JS, et al. A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology. Spine (Phila Pa 1976). 2005. 30(1): 15-24.
[17] Masuda K, Aota Y, Muehleman C, et al. A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine (Phila Pa 1976). 2005. 30(1): 5-14.
[18] Gruber HE, Johnson TL, Leslie K, et al. Autologous intervertebral disc cell implantation: a model using Psammomys obesus, the sand rat. Spine (Phila Pa 1976). 2002. 27(15): 1626-33.
[19] Olmarker K, Blomquist J, Stromberg J, Nannmark U, Thomsen P, Rydevik B. Inflammatogenic properties of nucleus pulposus. Spine (Phila Pa 1976). 1995. 20(6): 665-9.
[20] Satoh K, Konno S, Nishiyama K, Olmarker K, Kikuchi S. Presence and distribution of antigen-antibody complexes in the herniated nucleus pulposus. Spine (Phila Pa 1976). 1999. 24(19): 1980-4.
[21]姜为民,杨惠林.退变腰椎间盘组织的血管浸润现象及其意义.中华骨科杂志. 1998. (09): 24-26.
[22] BmWn T.Some mechanieal test on lumbo-sacral spine with particalar reference to the intervertebral disc:a preliminary report.Joint Srug,1957{39A:l135
[23] Adams MA,Hutt0n WC.The relevance of torsion to the mechenical derangemengt of the lumbar.Spine,1981 I6:241
[24] Hansson T.Bengt R.The relation between mineral compression fractures,and disc degeneration in lumbar vertebrace.Spine,1981;6:147
[25] Hunter C J.The notochordal cell in the nucleus pulposus:a review in the context oftissue engineering.Tissue Engineering,2003
[26] Haefeli M,Kalberer F,Saegesser D,et al Spine.2006:31(14):1522-1531;
[27] Freemont AJ.1e Maitre CL .Watkins A,et al.Expert Rev Mol Med.200l;2001:1-10.
[28] Gruber HE.Norton HJ.Ingram JA,et al.Spine,2005;30(6):625-630.
[29] Paul R.Haydon RC,Cheng H.et al.Spine.2003;28(8):755-763.
[30] Sekiya I.Tsuji K.Koopman P.et al.J Biol Chem.2000;275(15):10738-10744.
[31] Lotz M. CIin Orthop.200l;391(suppl):S108-S115.
[32] Kim KS.Yoon ST.Park JS.et al.J Neurosurg.2003;99(3 Suppl):291-297.
[33] Roughley P,Martens D.Rantakokko J.et al.Eur Cell Mater.2006:11:l-7.
[34] Omlor GW.Lorenz H.Engelleiter K.et al.J Orthop Res.2006:24(3):385-392.
[35] SilberbergR,Aufdermaur M, Adler JH.Degeneration of the intervertebral disksand spondylosis in aging sand rats. Arch Pathol Lab Med 1979;103(5):231–5.
[36] Adler JH, Schoenbaum M, Silberberg R. Early onset of disk degeneration and spondylosis in sand rats (Psammomys obesus). Vet Pathol 1983;20:13–22.
[37] Moskowitz RW, Ziv I, Denko CW, Boja B, Jones PK, Adler JH.Spondylosis in sand rats: a model of intervertebral disc degeneration and hyperostosis. J Orthop Res 1990;8:401–11.
[38] Ziv I, Moskowitz RW, Kraise I, Adler JH,Maroudas A. Physicochemical properties of the aging and diabetic sand rat intervertebral disc.J Orthop Res 1992;10:205–10.
[39] Ziran BH, Pineda S, Pokharna H, Esteki A, Mansour JM, Moskowitz RW. Biomechanical, radiologic, and histopathologic correlations in the pathogenesis of experimental intervertebral disc disease. Spine1994;19:2159–63.
[40] Gruber HE, Johnson T, Norton HJ, Hanley EN Jr. The sand rat model for disc degeneration: radiologic characterization of age-related changes: cross-sectional and prospective analyses. Spine 2002;27:230–4.
[41] Gruber HE, Johnson TL, Leslie K, et al. Autologous intervertebral disc cell implantation: a model using Psammomys obesus, the sand rat. Spine2002;27:1626–33.
[42] Berry R. Genetically controlled degeneration of the nucleus pulposus in the mouse. J Bone Joint Surg 1961;43B:387–93.
[43] Silberberg R, Gerritsen G. Aging changes in intervertebral discs and spondylosis in Chinese hamsters. Diabetes 1976;25:477–83.
[44] Cole TC, Ghosh P, Taylor TK. Variations of the proteoglycans of the canine intervertebral disc with ageing. Biochim Biophys Acta 1986;880:209–19.
[45] Goggin JE, Li AS, Franti CE. Canine intervertebral disk disease:characterization by age, sex, breed, and anatomic site of involvement.Am J Vet Res 1970;31:1687–92.
[46] Ghosh P, Taylor TK, Braund KG, Larsen LH. The collagenous and non-collagenous protein of the canine intervertebral disc and their variation with age, spinal level and breed. Gerontology 1976;22:124–34.
[47] Gillett NA, Gerlach R, Cassidy JJ, Brown SA. Age-related changes in the beagle spine. Acta Orthop Scand 1988;59:503–7.
[48] Lauerman WC, Platenberg RC, Cain JE, Deeney VF. Age-related disk degeneration: preliminary report of a naturally occurring baboon model. J Spinal Disord 1992;5:170–4.
[49] Goff C, Landmesser W. Bipedal rats and mice: laboratory animals for orthopaedic research. J Bone Joint Surg 1957;39A:616–22.
[50] Yamada K. The dynamics of experimental posture. Experimental study of intervertebral disk herniation in bipedal animals. Clin Orthop 1962;25:20–31.
[51] Higuchi M, Abe K, Kaneda K. Changes in the nucleus pulposus of the intervertebral disc in bipedal mice. A light and electron microscopic study. Clin Orthop 1983;175:251–7.
[52] Cassidy JD, Yong-Hing K, Kirkaldy-Willis WH, Wilkinson AA. A study of the effects of bipedism and upright posture on the lumbosacral spine and paravertebral muscles of the Wistar rat. Spine 1988;13:301–8.
[53] Hutton WC, Yoon ST, Elmer WA, et al. Effect of tail suspension (or simulatedweightlessness) on the lumbar intervertebral disc: study of proteoglycans and collagen. Spine 2002;27:1286–90.
[54] Lotz J, Colliou O, Chin J, Duncan N, Liebenberg E. Compressioninduced degeneration of the intervertebral disc: an in vivo mouse model and finite element study. Spine 1998;23:2493–506.
[55] Iatridis JC, Mente PL, Stokes IA, Aronsson DD, Alini M. Compression-induced changes in intervertebral disc properties in a rat tail model. Spine 1999;24:996–1002.
[56] Ching CT, Chow DH, Yao FY, Holmes AD. The effect of cyclic compression on the mechanical properties of the inter-vertebral disc:an in vivo study in a rat tail model. Clin Biomech (Bristol, Avon)2003;18:182–9.
[57] Kroeber MW, Unglaub F, Wang H, et al. New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration. Spine 2002;27:2684–90.
[58] Hadjipavlou AG, Simmons JW, Yang JP, Bi LX, Simmons DJ,Necessary JT. Torsional injury resulting in disc degeneration in the rabbit: II. Associative changes in dorsal root ganglion and spinal cord neurotransmitter production. J Spinal Disord 1998;11:318–21.
[59] Hadjipavlou AG, Simmons JW, Yang JP, et al. Torsional injury resulting in disc degeneration: I. An in vivo rabbit model. J Spinal Disord 1998;11:312–7.
[60] Miyamoto S, Yonenobu K, Ono K. Experimental cervical spondylosis in the mouse. Spine 1991;16(10 suppl):S495–500.
[61] Sullivan J, Farfan H, Kahn D. Pathologic changes with intervertebral joint rotational instability in the rabbit. Can J Surg 1971;14:71–9.
[62] Phillips FM, Reuben J, Wetzel FT. Intervertebral disc degeneration adjacent to a lumbar fusion. An experimental rabbit model. J Bone Joint Surg Br 2002;84:289–94.
[63] Keyes D, Compere E. The normal and pathological physiology of the nucleus pulposus of the intervertebral disc: an anatomical, clinical,and experimental study. J Bone Joint Surg 1932;14:897–938.
[64] Smith J, Walmsley R. Experimental incision of the intervertebral disc. J Bone Joint Surg 1951;33B:612–25.
[65] Haimovici EH. Experimental disc lesion in rabbits. The effect of repeated ACTH administration. Acta Orthop Scand 1970;41:505–21.
[66] Lipson SJ, Muir H. Experimental intervertebral disc degeneration:morphologic and proteoglycan changes over time. Arthritis Rheum1981;24:12–21.
[67] Urayama S. Histological and ultrastructural study of degeneration of the lumbar intervertebral disc in the rabbit following nucleotomy,with special reference to the topographical distribution pattern of the degeneration. Nippon Seikeigeka Gakkai Zasshi 1986;60:649–62.
[68] Masuda K, Aota Y, Muehleman C, et al. A novel rabbit model of mild, reproducible disc degeneration by an annulus needle puncture:correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine 2005;30:5–14.
[69] Aota Y, Masuda K, Nguyen C, Andersson G, Thonar EJ, An H.Radiological and MRI analyses of a novel rabbit model: A mild,progressive disc degeneration. Ortho Res Soc Trans 2002;27(abstr.):118.
[70] Muehleman C, Masuda K, Imai Y, et al. Histological assessment of a novel needle puncture model: a mild, progressive intervertebral disc degeneration. Ortho Res Soc Trans 2003;28(abstr.):86.
[71] Kompel J, Sobajima S, Clarke C, et al. MRI and histological analysis of a rabbit model of disc degeneration. Ortho Res Soc Trans 2003;28:253.
[72] Osti OL, Vernon-Roberts B, Fraser RD. 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model. Spine 1990;15:762–7.
[73] Kaapa E, Holm S, Han X, Takala T, Kovanen V, Vanharanta H.Collagens in the injured porcine intervertebral disc. J Orthop Res 1994;12:93–102.
[74] Kaapa E, Zhang LQ, Muona P, Holm S, Vanharanta H, Peltonen J.Expression of type I,III, and VI collagen mRNAs in experimentally injured porcine intervertebral disc. Connect Tissue Res 1994;30:203–14.
[75] Kaapa E, Gronblad M, Holm S, Liesi P, Murtomaki S, Vanharanta H.Neural elements in the normal and experimentally injured porcine intervertebral disk. Eur Spine J 1994;3:137–42.
[76] Pfeiffer M, Griss P, Franke P. Degeneration model of the porcine lumbar motion segment: effects of various intradiscal procedures. Eur Spine J 1994;3:8–16.
[77] Holm S, Holm AK, Ekstrom L, Karladani A, Hansson T. Experimental disc degeneration due to endplate injury. J Spinal Disord Tech 2004;17:64–71.
[78] Wada E, Ebara S, Saito S, OnoK. Experimental spondylosis in the rabbit spine. Overuse could accelerate the spondylosis. Spine 1992;17(3suppl):S1–6.
[79] Bradford DS, Cooper KM, Oegema TR Jr. Chymopapain, chemonucleolysis,and nucleus pulposus regeneration. J Bone Joint Surg Am 1983;65:1220–31.
[80] Bradford DS, Oegema TR Jr, Cooper KM, Wakano K, Chao EY.Chymopapain, chemonucleolysis, and nucleus pulposus regeneration.A biochemical and biomechanical study. Spine 1984;9:135–47.
[81] Kahanovitz N, Arnoczky SP, Kummer F. The comparative biomechanical,histologic, and radiographic analysis of canine lumbar discs treated by surgical excision or chemonucleolysis. Spine 1985;10:178–83.
[82] Spencer DL, Miller JA, Schultz AB. The effects of chemonucleolysis on the mechanical properties of the canine lumbar disc. Spine 1985;10:555–61.
[83] Nitobe T, Harata S, Okamoto Y, Nakamura T, Endo M. Degradation and biosynthesis of proteoglycans in the nucleus pulposus of canine intervertebral disc after chymopapain treatment. Spine 1988;13:1332–9.
[84] Takahashi T, Nakayama M, Chimura S, et al. Treatment of canine intervertebral disc displacement with chondroitinase ABC. Spine 1997;22:1435–9; discussion 46–7.
[85] Ono A, Harata S, Takagaki K, Endo M. Proteoglycans in the nucleus pulposus of canine intervertebral discs after chondroitinase ABC treatment.J Spinal Disord1998;11:253–60.
[86] Zook BC, Kobrine AI. Effects of collagenase and chymopapain on spinal nerves and intervertebral discs of cynomolgus monkeys. J Neurosurg 1986;64:474–83.
[87] Olmarker K, Rydevik B, Dahlin LB, Danielsen N, Nordborg C. Effects of epidural and intrathecal application of collagenase in the lumbar spine: an experimental study in rabbits. Spine 1987;12:477–82.
[88] Kato F, Iwata H, Mimatsu K, Miura T. Experimental chemonucleolysis with chondroitinase ABC. Clin Orthop 1990;301–8.
[89] Eurell JA, Brown MD, Ramos M. The effects of chondroitinase ABC on the rabbit intervertebral disc. A roentgenographic and histologic study. Clin Orthop 1990;256:238–43.
[90] Takahashi T, Kurihara H, Nakajima S, et al. Chemonucleolytic effects of chondroitinase ABCon normal rabbit intervertebral discs. Course of action up to 10 days postinjection and minimum effective dose. Spine 1996;21:2405–11.
[91] Sumida K, Sato K, Aoki M, Matsuyama Y, Iwata H. Serial changes in the rate of proteoglycan synthesis after chemonucleolysis of rabbit intervertebral discs. Spine 1999;24:1066–70.
[92] Takenaka Y, Revel M, Kahan A, Amor B. Experimental model of disc herniations in rats for study of nucleolytic drugs. Spine 1987;12:556–60.
[93] Norcross JP, Lester GE, Weinhold P, Dahners LE. An in vivo model of degenerative disc disease. J Orthop Res 2003;21:183–8.
[94] Sasaki M, Takahashi T, Miyahara K, Hirose AT. Effects of chondroitinase ABC on intradiscal pressure in sheep: an in vivo study. Spine 2001;26:463–8.
[95] Greg Anderson D, Li X, Tannoury T, Beck G, Balian G. A fibronectin fragment stimulates intervertebral disc degeneration in vivo. Spine 2003;28:2338–45.
[96] Oda H, Matsuzaki H, Tokuhashi Y, Wakabayashi K, Uematsu Y,Iwahashi M. Degeneration of intervertebral discs due to smoking:experimental assessment in a rat-smoking model. J Orthop Sci 2004;9:135–41.
[97] Iwahashi M, Matsuzaki H, Tokuhashi Y, Wakabayashi K, Uematsu Y.Mechanism of intervertebral disc degeneration caused by nicotine in rabbits to explicate intervertebral disc disorders caused by smoking.Spine 2002;27:1396–401.
[1] Humzah, M.D., and Soames, R.W. Human intervertebral disc: Structure and function. Anat. Rec. 220, 337, 1988.
[2] Holm, S.H. Nutritional and pathophysiologic aspects of the lumbar intervertebral disc. In: Wiesel, S.W., Weinstein, J.N., Herkowitz, H.N., Dvorak, J., and Bell, G.R., eds. The Lumbar Spine. Philadelphia, PA: W.B. Saunders, 1996, pp.285–310.
[3] DePalma, A.F., and Rothman, R.H. The Intervertebral Disc. Philadelphia, PA: W.B. Saunders, 1970.
[4] Iatridis, J.C., Weidenbaum, M., Setton, L.A., and Mow,V.C. Is the nucleus pulposus a solid or a fluid? Mechanical behaviors of the nucleus pulposus of the human intervertebral disc. Spine 21, 1174, 1996.
[5] Roberts, S., Menage, J., Duance, V., Wotton, S., and Ayad, S. Collagen types aroundthe cells of the intervertebral disc and cartilage end plate: An immunolocalization study. 1991 Volvo Award in Basic Sciences. Spine 16, 1030, 1991.
[6] Sztrolovics, R., Alini, M., Mort, J.S., and Roughley, P.J.
[7] Age-related changes in fibromodulin and lumican in human intervertebral discs. Spine 24, 1765, 1999.
[8] Melrose, J., Ghosh, P., and Taylor, T.K. A comparative analysis of the differential spatial and temporal distributions of the large (aggrecan, versican) and small (decorin, biglycan, fibromodulin) proteoglycans of the intervertebral disc. J. Anat. 198, 3, 2001.
[9] Trout, J.J., Buckwalter, J.A., Moore, K.C., and Landas,S.K. Ultrastructure of the human intervertebral disc. I.Changes in notochordal cells with age. Tissue Cell 14, 359,1982.
[10] Trout, J.J., Buckwalter, J.A., and Moore, K.C. Ultrastructure of the human intervertebral disc. II. Cells of the nucleus pulposus. Anat. Rec. 204, 307, 1982.
[11] Maldonado, B.A., and Oegema, T.R.J. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J. Orthop. Res. 10, 677, 1992
[12] Trout, J.J., Buckwalter, J.A., Moore, K.C., and Landas,S.K. Ultrastructure of the human intervertebral disc. I.Changes in notochordal cells with age. Tissue Cell 14, 359,1982.
[13] Trout, J.J., Buckwalter, J.A., and Moore, K.C. Ultrastructure of the human intervertebral disc. II. Cells of the nucleus pulposus. Anat. Rec. 204, 307, 1982.
[14] Stevens, J.W., Kurriger, G.L., Carter, A.S., and Maynard,J.A. CD44 expression in the developing and growing rat intervertebral disc. Dev. Dyn. 219, 381, 2000.
[15] Maldonado, B.A., and Oegema, T.R.J. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J. Orthop. Res. 10, 677, 1992.
[16] Fowlis, D., Colnot, C., Ripoche, M.A., and Poirier, F.Galectin-3 is expressed in the notochord, developing bones,and skin of the postimplantation mouse embryo. Dev. Dyn.203, 241, 1995.
[17] Domowicz, M., Li, H., Hennig, A., Henry, J., Vertel, B.M.and Schwartz, N.B. Thebiochemically and immunologically distinct CSPG of notochord is a product of the aggrecan gene. Dev. Biol. 171, 655,1995.
[18] Oganesian, A., Zhu, Y., and Sandell, L.J. Type IIA procollagen amino propeptide is localized in human embryonic tissues. J. Histochem. Cytochem. 45, 1469, 1997.
[19] Zhu, Y., McAlinden, A., and Sandell, L.J. Type IIA procollagen in development of the human intervertebral disc: Regulated expression of the NH2-propeptide by enzymic processing reveals a unique developmental pathway. Dev.Dyn. 220, 350, 2001.
[20] Brissett, N.C., and Perkins, S.J. The protein fold of the hyaluronate-binding proteoglycan tandem repeat domain of link protein, aggrecan and CD44 is similar to that of the C-type lectin superfamily. FEBS Lett. 388, 211, 1996.
[21] Watanabe, H., Cheung, S.C., Itano, N., Kimata, K., and Yamada,Y. Identification of hyaluronan-binding domains of aggrecan. J. Biol. Chem. 272, 28057, 1997.
[22] Hardingham, T.E., Fosang, A.J., and Dudhia, J. The structure, function and turnover of aggrecan, the large aggregating proteoglycan from cartilage. Eur. J. Clin. Chem. Clin. Biochem. 32, 249, 1994.
[23] Dong, S., and Hughes, R.C. Macrophage surface glycoproteins binding to galectin-3 (Mac-2-antigen). Glycoconj. J. 14, 267, 1997.
[24] Kuwabara, I., and Liu, F.T. Galectin-3 promotes adhesion of human neutrophils to laminin. J.Immunol. 156, 3939,1996.
[25] Sato, S., and Hughes, R.C. Binding specificity of a baby hamster kidney lectin for H type I and II chains, polylactosamine glycans, and appropriately glycosylated forms of laminin and fibronectin. J. Biol. Chem. 267,6983, 1992.
[26] Probstmeier, R., Montag, D., and Schachner, M. Galectin-3, a b-galactoside-binding animal lectin, binds to neural recognition molecules. J. Neurochem. 64, 2465, 1995.
[27] Hayes, A.J., Benjamin, M., and Ralphs, J.R. Role of actin stress fibres in the development of the intervertebral disc: Cytoskeletal control of extracellular matrix assembly. Dev.Dyn. 215, 179, 1999.
[28] Domowicz, M., Li, H., Hennig, A., Henry, J., Vertel, B.M.and Schwartz, N.B. Thebiochemically and immunologically distinct CSPG of notochord is a product of the aggrecan gene. Dev. Biol. 171, 655, 1995.
[1]Ogata K, Kur ki P , Celis J E , et al . Monoclonal a ntibodies to a nuclea r p rotein ( PCNA/ Cyclin) associated wit h DNA replication[J ] . Exp Cell Res ,1987 ,168 (2) :475 - 486.
[2] Van Dierendonck J H, Wijsman J H, Keijzer R , et al . Cell2cycle2related staining patterns of anti2proliferating cell nuclear antigen monoclonal antibodies. Comparison with BrdUrd labelling and Ki267 staining[J ] . Am J Pathol ,1991 ,138(5) :1165 - 1172.
[3] Takashi Tsuji, Kazuhiro Chiba, Hideaki Imabayashi, etc. Age-Related Changes in Expression of Tissue Inhibitor of Metalloproteinases-3 Associated With Transition From the Notochordal Nucleus Pulposus to the Fibrocartilaginous Nucleus Pulposus in Rabbit Intervertebral Disc. SPINE , 32(8), pp 849–856
[4] Christopher J. Hunter, John R. Matyas, Neil A. Duncan. Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison J. Anat. 2004,205, pp357–362.
[5] Pulposus Rodolfo Cappello, Joseph L. E. Bird, Dirk Pfeiffe, Notochordal CellProduce and Assemble Extracellular Matrix in a Distinct Manner, Which May Be Responsible for the Maintenance of Healthy Nucleus r. spine , 2006, 31(8), pp 873–882
[6]Christopher J. Hunter,John R. Matyas, Neil A. Duncan. The three-dimensional architecture of the notochordal nucleus pulposus: novel observations on cell structures in the canine intervertebral disc. J. Anat. 2003,202, pp279D291
[7] Horwitz, T. The human notochord: A study of its development and regression, variations, and pathologic derivative, chordoma. Indianapolis: 1977.
[8] Horwitz, T. The human notochord: A study of its development and regression, variations, and pathologic derivative, chordoma. Indianapolis: 1977.
[9] Maldonado, B.A., and Oegema, T.R.J. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J. Orthop. Res. 1992, 10, 677.
[10] Aguiar, D.J., Johnson, S.L., and Oegema, T.R. Notochordal cells interact with nucleus pulposus cells: Regulation of proteoglycan synthesis. Exp. Cell Res. 1999,.246, 129.
[11] Maldonado, B.A., and Oegema, T.R.J. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J. Orthop. Res. 1992 ,10, 677.
[12] Biochemical Society Transactions (2002) Volume 30, part 6 839-844 The role of disc cell heterogeneity in determining disc biochemistry: a speculation T. R. Oegema, Jr1
[13] Aguiar, D.J., Johnson, S.L., and Oegema, T.R. Notochordal cells interact with nucleus pulposus cells: Regulation of proteoglycan synthesis. Exp. Cell Res. 1999.246, 129.
[14] Adler JH, Schoenbaum M, Silberberg R(1983) Early onset of disk degeneration and spondylosis in sand rats (Psammomys obesus).Vet.Pathol.20, 13–22.
[15] Aguiar DJ, Johnson SL, Oegema TR(1999) Notochordal cells interact with nucleus pulposus cells: regulation of proteoglycan synthesis.Exp.Cell Res.246, 129–137.
[16] Anderson DG, Izzo MW, Hall DJ, et al.(2002) Comparative gene expression profiling of normal and degenerative discs:analysis of a rabbit annular laceration model.Spine.27,1291–1296.
[17] Ariga K, Miyamoto S, Nakase T, et al.(2001) The relationship between apoptosis ofendplate chondrocytes and aging and degeneration of the intervertebral disc.Spine.26, 2414–2420.
[18] Bell GR(1996) Anatomy of the lumbar spine: developmental to normal adult anatomy. In The Lumbar Spine(eds WieselSW, Weinstein JN, Herkowitz HN, Dvorak J, Bell GR), pp. 43–52.
[19] Bray JP, Burbidge HM(1998) The canine intervertebral disk.Part Two: Degenerative changes– nonchondrodystrophoid versus chondrodystrophoid disks.J.Am.Anim Hosp.Assoc.34, 135–144.
[20] Butler WF(1989) Comparative anatomy and development of the mammalian disc. In The Biology of the Intervertebral Disc(ed. Gosh P), pp. 84–108. Boca Raton: CRC Press.
[21] DePalma AF,Rothman RH(1970)The Intervertebral Disc, 1stedn. Philadelphia, PA: W.B. Saunders Company.
[22] Errington RJ, Puustjarvi K, White IR, Roberts S, Urban JP(1998)Characterisation of cytoplasm-filled processes in cells of the intervertebral disc.J.Anat.192, 369–378.
[23] Frick SL, Hanley EN, Meyer RA, JrRamp WK, JrChapmanTM(1994) Lumbar intervertebral disc transfer. A canine study.Spine19, 1826–1834.
[24] Ganey T, Libera J, Moos V, et al.(2003) Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc.Spine.28, 2609–2620.
[25] Hansen HJ(1952) A pathologic–anatomical study on disc degeneration in dog.Acta Orthop.Scand Suppl.11.
[26] Hansen HJ(1959) Comparative views on the pathology of disk degeneration in animals.Lab.Invest.8, 1242–1265.
[27] Hayes AJ, Benjamin M, Ralphs JR(2001) Extracellular matrix indevelopment of the intervertebral disc.Matrix Biol.20, 107–121.
[28] Holm SH(1996) Nutritional and pathophysiologic aspects of the lumbar intervertebral disc. In The Lumbar Spine(edsWiesel SW, Weinstein JN, Herkowitz HN, Dvorak J, Bell GR),pp. 285–310. philadelphia, PA: W.B. Saunders Company.
[1] Lob A, Holm C. Dic zusammenhange zwisehen den verletzungen der bandscheiben and der spondylosis deformans im tierversuch. Dtsch Ztschr Chr, 1933, 240:421-440.
[2] Key JA, Ford LT. Experimental intervertebral-disc lesions. J Bone Joint Surg(Am),1948, 30:621-629.
[3] Hansen HJ. A pathologic-anatomical study on disc degeneration in dogs. Acta Orthop Scand(Br),1952, 11(suppl 3):111-117.
[4] Berry RJ. Genetically controlled degeneration of the nucleus pulposus in the mouse. J Bone Joint Surg(Br), 1961, 43:387-393.
[5] Gillett NA,Gerlach R,Cassidy JJ,et a1.Age-related changes in the beagle spine[J].Acta Orthop Scand,1988,59:503-507.
[6] Silberberg R, Aufdermaur M, Adler JH.Degeneration of the intervetebral disks and spondylosis in aging sand rats. Arch Pathol Lab Med, 1979, 103:231 -235.
[7] Osti OL, Vernon -Roberts B, Fraser RD, et al. 1990 Volvo Award in experimenta studys. Anulus tears and intervertebral disdegeneration:an experimental study using an animal model. Spine, 1990, 15:762-767.
[8] Nguyen CM, Haughton VM, Ho KC, et al. A model for studying intervertebral disc degeneration with magnetic resonace and a nucletome. Invest Radiol, 1989, 24:407-409.
[9] Lipson SJ, Muir H. Proteoglycans in experimental intervertebral disc degeneration. Spine, 1981, 6:194-210.
[10] Keyes DC, Compere EL. The normal and pathological physiolgy of the nucleus pulposus of the intervertebral disc:an anatomical,clinical, and experimental study. J Bone Joint Surg(Br), 1932, 14:897 -938.
[11] Bercovici S, Paraschivesco E. Recherche experimentale sur ladiscopathie vertebrale degenerative. Rev Rheum, 1958, 25:487 -499.
[12] Lu DS,Luk KD,Lu W,et a1.Spinal flexibility in ovease after chymopapain injectionis dose dependent:a possible alteract to antervior release in sodisis [J].Spine,2004,29:123-128
[13] Norcross JP,Lester GE,Weinhdd,et a1.An in vivo model of degenerative disc disease[J].J Orthop Res,2003,21:183—188.
[14] Greg-Anderson D. A fibronectin fragment stimulates intervertebral disc degeneration in vivo[J].Spine,2003,28:2338—2345.
[15] Cassidy JD , Yong-Hing K, Kirkaldy- Willis WH, et al. A study of the effects bipedism and upright posture on the lumbosacral spine and paravertebral muscles of the Wistar rat. Spine, 1988, 13:301 -308.
[16] Sullivan JD, Farfan HF, Kahn DS. Pathologic changes with intervertebral joint rotational instability in the rabbit. Can J Surg, 1971,14:71 -79.
[17] Lindblom K. Intervertebral -disc degeneration considered as a pressure atrophy . J Bone Joint Surg(Am), 1957, 39:933 -945.
[18] Wada E, Ebara S, Saito S, et al. Experiment spondylosis in the rabbit spine:overuse could accelerate the spondylosis. Spine, 1992, 17(suppl 3):1 -6.
[19] Schendel MJ, Dekutoski MB, Ogilvie JW,et al. Kinematics of the canine lumbar intervertebral joint:an in vivo study before and after adjacent instrumentation. Spine, 1995,20:2555 -2564.
[20] Cole TC, Burkhardt D, Ghosh P, et al. Effects of spinal fusion on the proteoglycans of the canine intervertebral disc. J Orthop Res,1985, 3:277 -291.
[21] Oda H,Matsuzaki H,Tokuhashi Y,et a1.Degeneration of intervertebral discs due to smoking:experimental assessment in a rat-smoking model[J].J Orthop Sci,2004,9(2):135—141.
[22] Wang T,Zhang L,Huang C,et a1.Relationship between osteopenia and lumbar intervcrtebral disc degeneration in ovariectomized rats[J].Calcif Tissue I nt,2004,75(3):205—213.
[23] Haefeli M,Kalberer F,Saegesser D,et al Spine.2006:31(14):1522-1531;
[24] Freemont AJ.1e Maitre CL .Watkins A,et al.Expert Rev Mol Med.200l;2001:1-10.
[25] Weiler C,Nerlich AG,Bachmeier BE.et al.Spine.2005;30(1):44-53.
[26] le Maitre CL, Freemont AJ, Hoyland JA. Arthritis Res Ther.2005:7(4):R732-R745]
[27] le Maitre CL, Freemont AJ, Hoyland JA. Int J Exp Pathol, 2006,87(1):17-28.
[28] Maeda S, Kokubun S. Spine,2000;25(2):166-169.
[29] Specchia N.Pagnotta A,Toesca A.et al.Eur Spine J.2002;11(2):145-151.
[30] Moroney P.Waston RWG.Burke JG.et al.PH and inflammatory mediators modulate nucleus puposus cytokine secretion.12th Annual Metting of European Orthopedic Research Society.Lausanne,Switzerland,2002:1-32.
[31] Rannou F.Corvol MT.Hudry C.et al.Spine,2000;25(1):l 7-23.
[32] Shen B,Melrose J.Ghosh P,et al.Eur Spine J.2003;12(1):66-75.
[33] Liu GZ.Ishihara H.Osada R.et al.Spine,200l:26(2):134-141.
[34] Kohyama K.Saura R.Doita M,et al.Kobe J Med Sci.2000;46(6):283-295.
[35] Haro H, Crawford HC, Fingleton B,et al. Matrix metallop roteinase-3-dependent generation of a macrophage chemoattractant in model of hermiated disc resorption[ J ]. J Clin Invest, 2000, 105 (2) : 133-141.
[36] Wallach CJ, Sobajima S,Watanabe Y, et al. Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs[ J ]. Spine, 2003, 28 (20) : 2331-2337.
[37] Le Maitre CL. Freemont AJ. Hoyland JA. Localization of degradable enzymes and their inhibitors in the degenerate human intervertebral disc[ J ]. J Pathol, 2004, 24 (1) : 47-54.
[38] Nishida T. Kinetics of tissue and serum matrix metalloproteinase-3 and tissue inhibitor of metalloprotiinases-1 in intervetebral disc degeneration and disc hermiation [ J ]. Kurume Med J, 1999, 46 (1) 39-50.
[39] Sobajima S, Shimer AL, Chadderdon RC, et al. Quantitative analysis of gene expression in a rabbit model of intervertebral disc degeneration by real-time polymerase chain reaction [ J ]. Spine, 2005, 5 (1) : 14-23.
[40] Masuda K, Imai Y, Okuma M, et al. Spine,2006;31(7):742-754.
[41] Tolonen J.Gronblad M,Vanharanta H.et al.Eur Spine J.2006;15(5):588-596.
[42] Wa1lach CJ.Gilbertson LG.Kang JD.Spine.2003;28(15 Suppl):S93-S98.
[43] Zhang Y,Li Z.Thonar EJ.et al.Spine.2005;30(23):260l-2607.
[44] Tim-Yoon S.Su-Kim K,Li J.et al,Spine.2003;28(16):1773-1780.
[45] Paassilta P.Lohiniva J,Goring HH.et al.JAMA.2001;285(14):1843-1849.
[46] Jim JJ.Noponen-Hietala N,Cheung KM.et al.Spine.2005;30(24):2735-2742.
[47] Gruber HE.Norton HJ.Ingram JA,et al.Spine,2005;30(6):625-630.
[48] Paul R.Haydon RC,Cheng H.et al.Spine.2003;28(8):755-763.
[49] Sekiya I.Tsuji K.Koopman P.et al.J Biol Chem.2000;275(15):10738-10744.
[50] Lotz M. CIin Orthop.200l;391(suppl):S108-S115.
[51] Kim KS.Yoon ST.Park JS.et al.J Neurosurg.2003;99(3 Suppl):291-297.
[52] Roughley P,Martens D.Rantakokko J.et al.Eur Cell Mater.2006:11:l-7.
[53] Omlor GW.Lorenz H.Engelleiter K.et al.J Orthop Res.2006:24(3):385-392.
[54] Kanemoto M,Hukuda S,Komiya Y,et al. Immunohistochemical study of Matrix Metalloproteinase-3 and Tissue Inhibitor of Metallo proteinase-1 in human intervertebral discs[J]. Spine,1996,21:1-8.
[55] MuIIer-Ladner U,Roberts CR,Franklin BN,et al. Human IL-1 Ra gene transfer into human synovial fibroblasts is chondroprotective[J]. J Immunol. 1997,158:3492—3498.
[56] Bandara G,Mueller GM,Galea-Lauri J,et al. Intraarticular expression of biologically active interleukin 1-receptor-antagonist protein by ex vivo gene transfer[J]. Proc Natl Acad Sci USA,1993,90:10764-10768.
[57] Olmarker K,Rydevik B.Selective inhibition of tumor necrosis factoralpha prevents nucleus pulposus-induced thrombus formation, intraneuraI edema, and reduction of nerve conduction velocity:possible implications for future pharmacologic treatment strategies of sciatica[J]. Spine,2001,26:863-869.
[58] Thompson JP,Oegema TR Jr,Bradford DS.Stimulation of mature canineintervertebral disc by growth factors.Spine,1991,16:253—260.
[59] Okuda S,Myoui A,Ariga K,et a1.Mechanisms of age-related decline in insulin-like growth factor-I dependent proteoglycan synthesis in rat intervertebral disc cells.Spine,2001,26:2421—2426.
[60] Gmber HE,Norton HJ,Hanley EN Jr.Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro.Spine,2000.25:2153—2157.
[61] Matsunaga S,Nagano S,Onishi T,et al. Age-related change in expression of transforming growth factor-beta and receptors in cells of intervertebral discs[J].J Neurosurg Spine,2003,98:63-67.
[62] Nishida K,Kang JD,Gilbertson LG,et al. Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy:an in vivo study of adenovirus-mediated transfer of the human transforming growth factor beta 1 encoding gene[J]. Spine.1999.24:2419—2425.
[63] Tan Y,Hu Y,Tan J.Extracellular matrix synthesis and ultrastructural changes of degenerative disc cells transfected by Ad/CMV—hTGFbeta 1[J]. Chin Med J(Engl),2003,116:1399—1403.
[64] Walsh AJL,Bradford DS,Lotz JCS. In vivo growth factor treatment of degenerated intervertebral discs[J]. Spine,2004,29:156-163.
[65] Yoon ST,Kim K,Li J,et al. The effect of bone morphogenetic protein-2 on rat intervertebral disc cells in vitro[J]. Spine,2003,28:1773-1780.
[66] Kim KS,Yoon ST,Park JS,et al. Inhibition of proteoglycan and type II collagen synthesis of disc nucleus cells by nicotine [J]. Spine,2003,99:291—297.
[67] Kim DJ,Moon SH,Kim H,et a1.Bone morphogenetic protein-2 facilitates expression of chondrogenic,not osteogenic,phenotype of human intervertebral disc cells[J]. Spine,2003,28:2679-2684.
[68] Moon S,Lee H,Park M,et al. BMP-2 upregulates the mRNA expression of aggrecan,collagen type I,and collagen type II in human intervertebral disc cells. in:Transactions of the 48th Annual Meeting of the Orthopaedic Research Society,Vol27,Dallas.TX.February 10-13, 2002.
[69] Takegami K,Thonar EJ,An HS,et a1.Osteogenic protein一1 enhances matrix replenishment by intervertebral disc cells previously exposed to interleukin一1.Spine,2002,27:1318—1325.
[70] ZhangY,An HS,Song S,et a1.Growthfactor osteogenic protein一1:differing effects on cells fromthree distinct zones in the bovine intervertebral disc.Am J Phys Med Rehabil,2004,83:515—521.
[71] Chang SC,Hoang B,Thomas JT,et a1.Cartilage—derived morphogenetic proteins . New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development.J Biol Chem,1994,269:28227—28234.
[72] Li J,Kim KS,Park JS,et a1.BMP一2 and CDMP一2:stimulation of chondrocyte production of proteoglycan.J Orthop Sci,2003,8:829—835.
[73] Walsh AJL,Bradford DS,Lotz JCS. In vivo growth factor treatment of degenerated intervertebral discs[J]. Spine,2004,29:156-163.
[74] Wang H,Kroeber M,Hanke M,et al. Release of active and depot GDF-5 after adenovirus-mediated overexpression stimulates rabbit and human intervertebral disc cells[J].J Mol Med.2004.82:126—134.
[75] Mwale F,Demers CN,Petit A,et a1.A synthetic peptide of link protein stimulates the biosynthesis of collagens II,IX and proteoglyean by cells of the intervertebral disc.J Cell Bioehem,2003,88:1202一l213.
[76]Yoon ST,Kim K,Li J,et al. The effect of bone morphogenetic protein-2 on rat intervertebral disc cells in vitro[J]. Spine,2003,28:1773-1780.
[77] Paul R,Haydon RC,Cheng H,et al. Potential use of sox9 gene therapy for intervertebral degenerative disc disease[J]. Spine,2003.28:755—763.
[78] Israel DI,Nove J,Kems KM et a1.Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo.Growth Factors,1996,13:291—300.
[1] Kim KW, Lim TH, Kim JG, Jeong ST, Masuda K, An HS. 2003. The origin of chondrocytes in the nucleus pulposus and histologic findings associated with the transition of a notochordal nucleus pulposus to a fibrocartilaginous nucleus pulposus in intact rabbit intervertebral discs. Spine 28:982–990.
[2] Kuro-o M, Matsumura Y, Aizawa H,Kawaguchi H, Suga T, Utsugi T,Ohyama Y, Kurabayashi M,Kaname T,Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI.1997. Mutation of the mouse klotho gene leads to a syndrome resembling ageing.Nature 390:45–51.
[3] Maldonado BA, Oegema TR, Jr. 1992. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J Orthop Res 10:677-690.
[4] Humzah, M.D., and Soames, R.W. Human intervertebral disc: Structure and function. Anat. Rec. 220, 337, 1988.
[5] Holm, S.H. Nutritional and pathophysiologic aspects of the lumbar intervertebral disc. In: Wiesel, S.W., Weinstein,J.N., Herkowitz, H.N., Dvorak, J., and Bell, G.R., eds. The Lumbar Spine. Philadelphia, PA: W.B. Saunders, 1996, pp.285–310.
[6] DePalma, A.F., and Rothman, R.H. The Intervertebral Disc.Philadelphia, PA: W.B. Saunders, 1970.
[7] Iatridis, J.C., Weidenbaum, M., Setton, L.A., and Mow,V.C. Is the nucleus pulposus asolid or a fluid? Mechanical behaviors of the nucleus pulposus of the human intervertebral disc. Spine 21, 1174, 1996.
[8] Roberts, S., Menage, J., Duance, V., Wotton, S., and Ayad,S. Collagen types around the cells of the intervertebral disc and cartilage end plate: An immunolocalization study. 1991 Volvo Award in Basic Sciences. Spine 16, 1030, 1991.
[9] Sztrolovics, R., Alini, M., Mort, J.S., and Roughley, P.J.Age-related changes in fibromodulin and lumican in human intervertebral discs. Spine 24, 1765, 1999.
[10] Melrose, J., Ghosh, P., and Taylor, T.K. A comparative analysis of the differential spatial and temporal distributions of the large (aggrecan, versican) and small (decorin,biglycan, fibromodulin) proteoglycans of the intervertebral disc. J. Anat. 198, 3, 2001.
[11] Trout, J.J., Buckwalter, J.A., Moore, K.C., and Landas,S.K. Ultrastructure of the human intervertebral disc. I.Changes in notochordal cells with age. Tissue Cell 14, 359,1982.
[12] Trout, J.J., Buckwalter, J.A., and Moore, K.C. Ultrastructure of the human intervertebral disc. II. Cells of the nucleus pulposus. Anat. Rec. 204, 307, 1982.
[13] Videman, T., and Battie, M.C. Epidemiology of disc disease.In: Wiesel, S.W., Weinstein, J.N., Herkowitz, H.N.,Dvorak, J., and Bell, G.R., eds. The Lumbar Spine. Philadelphia,PA: W.B. Saunders, 1996, pp. 16–27.
[14] Andersson, G.B. The epidemiology of spinal disorders. In:Frymoyer, J.W., ed. The Adult Spine. Philadelphia, PA:Lippincott, 1997.
[15] Frymoyer, J.W. Magnitude of the problem. In: Wiesel,S.W., Weinstein, J.N.,Herkowitz, H.N., Dvorak, J., and Bell, G.R., eds. The Lumbar Spine. Philadelphia, PA: W.B.Saunders, 1996, pp. 8–15.
[16] Pope, M.H. Occupational hazards for low back pain. In:Frymoyer, J.W., ed. The Adult Spine. Philadelphia, PA:Lippincott, 1997.
[17] Wang WL,Abramson JH,Ganguly A,et a1.The surgical pathology of notochordal remnants in adult intervertebral disks:a report of 3 cases[J].Am J Surg Pathol,2008,32 (8)l123-l129.
[18] Le Maitre CL,Freemont AJ,Hoyland JA.Accelerated cellular senescence in degenerate intervertebral discs:a possible role in the pathogenesis of intervertebral disc degeneration l J1.Arthritis Res Ther.2007,9(3):R45.
[19] Hunter CJ,Matyas JR,Duncan NA.The functional significance of cell clusters in the notochordal nucleus pulposus:survival and signaling in the canine intervertebral disc[J[.Spine,2004,29(10):1099～l104.
[20] Hunter CJ,Bianchi S,Cheng P,et a1.Osmoregulatory function of large vacuoles found in notochordal cells of the intervertebral disc running title:an osmoregulatory vacuole lJJ.Mol Cell Biomeeh,2007,4(4):227—237.
[21] Aguiar DJ,Johnson SL,Oegema TR.Notochordal cells interact with nucleus pulposus cells:regulation of proteoglycan synthesis[J].Exp Cell Res,1999,246(1):129—137.
[22] Chen J, Yan W ,Setton LA.Molecular phenotypes of notochordal cells purified from immature nucleus pulposus fJ.Eur Spine J,2006,15(Suppl 3):$303-311.
[23] Oguz E,Tsai TI",Di Martino A,et a1.Galectin-3 expression in the intervertebral disc:a useful marker of the notochord phenotype[J]?Spine,2007,32(1):9-16.
[24] Hunter CJ , Matyas JR , Duncan NA . Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus:a species comparison[J].J Anat,2004,205(5):357-362.
[25] Hunter CJ,Matyas JR,Duncan NA.The three—dimensional architeeture of the notoehordal nucleus pulposus:novel observations on cell structures in the canine intervertebral disc]J].J Anat,20o3,202(Pt 3):279—291.
[26] Guehring T,Urban JP,Cui Z, et a1.Noninvasive 3D vital imaging and characterization of notochordal cells of the intervertebral disc by femtoseeond near——infrared two——photon laser scanning microscopy and spatial—volume rendering[J].Mierosc Res Teeh,2008,71(4):298—304.
[27]赵献峰,刘浩,丰干均,等.脊索细胞促进髓核软骨样细胞增殖及表型维持Ⅲ.中国修复重建外科杂志,2008,22 (8):939～943.
[28] Aguiar DJ,Johnson SL,Oegema TR.Notochordal cells interactwith nucleus pulposus cells:regulation of proteoglyean synthesis[J].Exp Cell Res,1999,246(1):129-137.
[29] Smits P,l~febvre V.Sox5 and Sox6 are required for uotochord extraeellular matrix sheath formation,notochord cell survival and development of the nucleus pulposus of intervertebral discs[J[.Development,2003,130(6):1135-1148.
[30] Erwin W M ,Ashman K,0 Donnel P,et a1. Nucleus pulposus notoehord cells secrete connective tissue growth factor and up—regulate proteoglycan expression by intervertebral disc chondrocytes[J].Arthritis Rheum,2006,54(12):3859—3867.
[31] Ali R,Le Maitre CL,Richardson SM,et a1.Connective tissue growth factor expression in human intervertebral disc : implications for angiogenesis in intervertebral disc degeneration[J].Biotech Histochem,2008,83(5):239—245.
[32] Erwin WM.1nman RD.Notochord cells regulate intervertebral disc chondrocyte proteoglycan production and cell proliferation[J].Spine,2006,31(10):1094-1099.
[33] Cappello R,Bird JL,Pfeifer D,et a1.Notochordal cell produce and assemble extracellular matrix in a distinct manner,which may be responsible for the maintenance of healthy nucleus pulposus[J].Spine,2006,31(8):873—882;discussion 883.
[34] Inui Y,Nishida K,Doita M, et a1.Fas-ligand expression Oil nucleus pulposus begins in developing embryo[J].Spine,2004,29(21):2365—2369.
[35] Kim KW ,Kim YS,Ha KY , et a1.An autoerine or paracrine Fas—mediated counterattack: potential mechanism for apoptosis of notoehordal cells in intact rat nucleus pulposus[J].Spine,2005,30(11):1247—1251.
[36] Kim KW ,Ha KY,Lee JS,et a1.The apoptotie effects of oxidative stress and antiapoptotic effects of easpase inhibitors on rat notoehordal cells[J].Spine,2007,32(22):2443—2448.
[37]张学森,丁惠强.退变颈椎间盘组织中细胞凋亡及相关蛋白Caspase一8、Caspase-9的表达fJJ.宁夏医学杂志,2008,30(4):295—297.
[38] 0 halloran DM ,Pandit AS.Tissue—engineering approach to regenerating theintevertebral disc [J].Tissue Eng,2007,13(8):1927—1954.
[39] Nesti IJ,Li WJ.Shanti RM.et a1.Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous seatfold (HANFS) amalgam[J].Tissue Eng Part A,2008,14(9):1527-1537
[40]Nishida K, Kang JD,Gilbertson LG,et a1. Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy:an study of adenovims·mediated transfer of the human transforming growth factor beta 1 encoding gene.Spine,1999,24:2419-2425.
[41]Nishida K, Kang JD,Suh JK,et a1.Adenovims-mediated gene transfer to nucleus pulposus ceHs : implications for the treatment of intervertebral disc degeneration.Spine。1998.23:2437-2443.
[42]Maldonado BA,Oegema TR Jr.Initial characterization of the metabolism of intervertebral disc ceHs encapsulated in miemspheres.J Orthop Res,1992,10:677-690.
[43]Wang IY, Baer AE,KIlns VB。et a1. Intervertebral disc ceUs exhibit diferences in gene expression in alginate and monolayer culture.Spine,20o1.26:1747.1751.
[44]Gan JC,Dueheyne P,Vresilovie EJ。et a1.Intervertebral disc tissue engineering II:cultures of nucleus pulposus cells.Clin Orthop Relat Res,20o3,(411):315-324.
[45]Gan JC,Dueheyne P,Vresilovie EJ。eta1.Intervertebral disc tissue engineering I:characterization of the nucleus pulposus.Clin Orthop Relat Res,2003。(4l1):305-314.
[46]Poiraudean S, Monteiro I, Anraet P. et a1. Phenoty0ic characteristics of rabbit intervertebral disc cells . Comparison with cartilage cells from the$~lTle animals.Spine. 1999.24:837-844.
[47]Gruber HE,Fisher EC Jr,Desai B。et a1.Human intervertebral disc cels from the ann Ius:three-dimensional culture in agaros or alginate and responsiveness to TGF-beta1.Exp Ceu Res.1997.235:13-21.
[48]Ra.vlnou F,Poiraudean S,FohzV。eta1.Monolayerannhsfibrosus cell cultures ina mechanically active environment:local culture condition adaptations and cel phenotype study. J Lab Clin Med,2Ooo.136 :412.421.
[49]AUIIi M ,LiW ,Markovic P,eta1.The potential andlimitations ofa cel1.seeded eolagen hyaluronan scafold to engineer an intervertebral disc-like matrix.Spine,20o3,28:446-454.
[50] Omlor GW, Lorenz H, Engelleiter K, et al. Changes in gene expression and protein distribution at different stages of mechanically induced disc degenerationan in vivo study on the New Zealand white rabbit. J Orthop Res2006;24:385–92.
[51] Mankin HJ, Lippiello L. The turnover of adult rabbit articular cartilage.J Bone Joint Surg Am 1969;51:1591–600.
[52] Watanabe H, Yamada Y, Kimata K. Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function. J Biochem (Tokyo)1998; 124:687–93.
[53] Verzijl N, DeGroot J, Thorpe SR, et al. Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem 2000;275:39027–31.
[54] Roughley PJ. Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix. Spine 2004;29:2691–9.
[55] Paul R, Haydon RC, Cheng H, et al. Potential use of Sox9 gene therapy for intervertebral degenerative disc disease. Spine 2003;28:755–63.
[56] Gruber HE, Norton HJ, Ingram JA, et al. The SOX9 transcription factor in the human disc: decreased immunolocalization with age and disc degeneration.Spine 2005;30:625–30.
[57] Kim DJ, Moon SH, Kim H, et al. Bone morphogenetic protein-2 facilitates expression of chondrogenic, not osteogenic, phenotype of human intervertebral disc cells.Spine 2003;28:2679–84.
[58] Thompson JP, Oegema TR Jr, Bradford DS. Stimulation of mature canine intervertebral disc by growth factors. Spine 1991;16:253–60.
[59] Shimer AL, Sobajima S, C. CR, et al. BMP-2 gene transfer favorably alters course ofdisc degeneration in rabbit model. Orthopaedic Research Society:Washington DC,ME,2005;0183.
[60] Peng B, Hao J, Hou S, et al. Possible pathogenesis of painful intervertebral disc degeneration. Spine 2006;31:560–6.
[2] Hunter CJ, Matyas JR, Duncan NA. The notochordal cell in the nucleus pulposus: a review in the context of tissue engineering. Tissue Eng. 2003. 9(4): 667-77.
[3] Wasiak R, Pransky GS, Webster BS. Methodological challenges in studying recurrence of low back pain. J Occup Rehabil. 2003. 13(1): 21-31.
[4] Gilbertson L, Ahn SH, Teng PN, Studer RK, Niyibizi C, Kang JD. The effects of recombinant human bone morphogenetic protein-2, recombinant human bone morphogenetic protein-12, and adenoviral bone morphogenetic protein-12 on matrix synthesis in human annulus fibrosis and nucleus pulposus cells. Spine J. 2008. 8(3): 449-56.
[5] Hunter CJ, Matyas JR, Duncan NA. Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison. J Anat. 2004. 205(5): 357-62.
[6] Guehring T, Nerlich A, Kroeber M, Richter W, Omlor GW. Sensitivity of notochordal disc cells to mechanical loading: an experimental animal study. Eur Spine J. 2010. 19(1): 113-21.
[7] Mwale F, Wang HT, Petit A, et al. The effect of novel nitrogen-rich plasma polymer coatings on the phenotypic profile of notochordal cells. Biomed Eng Online. 2007. 6: 33.
[8] Erwin WM, Inman RD. Notochord cells regulate intervertebral disc chondrocyte proteoglycan production and cell proliferation. Spine (Phila Pa 1976). 2006. 31(10): 1094-9.
[9] Erwin WM. The Notochord, Notochordal cell and CTGF/CCN-2: ongoing activity from development through maturation. J Cell Commun Signal. 2008. 2(3-4): 59-65.
[10] Erwin WM, Ashman K, O'Donnel P, Inman RD. Nucleus pulposus notochord cells secrete connective tissue growth factor and up-regulate proteoglycan expression by intervertebral disc chondrocytes. Arthritis Rheum. 2006. 54(12): 3859-67.
[11] Rastogi A, Thakore P, Leung A, et al. Environmental regulation of notochordal geneexpression in nucleus pulposus cells. J Cell Physiol. 2009. 220(3): 698-705.
[12] Boyd LM, Chen J, Kraus VB, Setton LA. Conditioned medium differentially regulates matrix protein gene expression in cells of the intervertebral disc. Spine (Phila Pa 1976). 2004. 29(20): 2217-22.
[13] Masuda K, Imai Y, Okuma M, et al. Osteogenic protein-1 injection into a degenerated disc induces the restoration of disc height and structural changes in the rabbit anular puncture model. Spine (Phila Pa 1976). 2006. 31(7): 742-54.
[14] Horwitz, T. The human notochord: A study of its development and regression, variations, and pathologic derivative,chordoma. Indianapolis: 1977.
[15] Adler, J.H., Schoenbaum, M., and Silberberg, R. Early onset of disk degeneration and spondylosis in sand rats (Psammomys obesus). Vet. Pathol. 20, 13, 1983.
[16] Moskowitz, R.W., Ziv, I., Denko, C.W., Boja, B., Jones,P.K., and Adler, J.H.Spondylosis in sand rats: A model of intervertebral disc degeneration and hyperostosis. J. Orthop.Res. 8, 401, 1990.
[17] Hansen, H.J. A pathologic–anatomical study on disc degeneration in dog. Acta Orthop. Scand. Suppl. 11, 1952.
[18] Maldonado, B.A., and Oegema, T.R.J. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J. Orthop. Res. 10, 677, 1992.
[19] Scott, N.A., Harris, P.F., and Bagnall, K.M. A morphological and histological study of the postnatal development of intervertebral discs in the lumbar spine of the rabbit. J. Anat. 130, 75, 1980.
[20] Smith, J.W., and Serafini-Fracassini, A. The distribution of the proteinpolysaccharide complex in the nucleus pulposus matrix in young rabbits. J. Cell Sci. 3, 33, 1968.
[21] Kathmann, I., Cizinauskas, S., Rytz, U., Lang, J., and Jaggy, A. Spontaneous lumbar intervertebral disc protrusion in cats: Literature review and case presentations. J. Feline Med. Surg. 2, 207, 2000.
[22] Hansen, H.J. Comparative views on the pathology of disk degeneration in animals. Lab. Invest. 8, 1242, 1959.
[23] Butler, W.F. Comparative anatomy and development of the mammalian disc. In: Gosh, P., ed. The Biology of the Intervertebral Disc. Boca Raton, FL: CRC Press, 1989, pp.84–108.
[24]Carlier, E.W. The fate of the notochord and development of the intervertebral disc in the sheep. J. Anat. Phys. 24,573, 1890.
[1] Choi KS, Cohn MJ, Harfe BD. Identification of nucleus pulposus precursor cells and notochordal remnants in the mouse: implications for disk degeneration and chordoma formation. Dev Dyn. 2008. 237(12): 3953-8.
[2] Singh K, Masuda K, An HS. Animal models for human disc degeneration. Spine J. 2005. 5(6 Suppl): 267S-279S.
[3] Alini M, Eisenstein SM, Ito K, et al. Are animal models useful for studying human disc disorders/degeneration. Eur Spine J. 2008. 17(1): 2-19.
[4] Hunter CJ, Matyas JR, Duncan NA. Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison. J Anat. 2004. 205(5): 357-62.
[5] Kroeber MW, Unglaub F, Wang H, et al. New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration. Spine (Phila Pa 1976). 2002. 27(23): 2684-90.
[6] Sobajima S, Kompel JF, Kim JS, et al. A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology. Spine (Phila Pa 1976). 2005. 30(1): 15-24.
[7] Colloca CJ, Keller TS, Moore RJ, Harrison DE, Gunzburg R. Validation of a noninvasive dynamic spinal stiffness assessment methodology in an animal model of intervertebral disc degeneration. Spine (Phila Pa 1976). 2009. 34(18): 1900-5.
[8] Melrose J, Smith SM, Fuller ES, et al. Biglycan and fibromodulin fragmentation correlates with temporal and spatial annular remodelling in experimentally injured ovine intervertebral discs. Eur Spine J. 2007. 16(12): 2193-205.
[9] Melrose J, Ghosh P, Taylor TK, Latham J, Moore R. Topographical variation in the catabolism of aggrecan in an ovine annular lesion model of experimental disc degeneration. J Spinal Disord. 1997. 10(1): 55-67.
[10] Hoogendoorn RJ, Wuisman PI, Smit TH, Everts VE, Helder MN. Experimental intervertebral disc degeneration induced by chondroitinase ABC in the goat. Spine (Phila Pa 1976). 2007. 32(17): 1816-25.
[11]张闻力,刘浩,李坛珠.椎间盘退变动物模型的研究进展.中国修复重建外科杂志. 2007. 21(11): 1259-1262.
[12]屈开钛(综述),徐永清(审校),王非(审校).实验介导椎间盘退变动物模型的研究进展.昆明医学院学报.2008,29(B06).-219-223.昆明医学院学报.2008,29(B06).-219-223(昆明医学院学报.2008,29(B06).-219-223):昆明医学院学报.2008,29(B06).-219-223.
[13] Cassidy JD, Yong-Hing K, Kirkaldy-Willis WH, Wilkinson AA. A study of the effects of bipedism and upright posture on the lumbosacral spine and paravertebral muscles of the Wistar rat. Spine (Phila Pa 1976). 1988. 13(3): 301-8.
[14] Waters PM, Lipson SJ. Modification of the degenerative response in experimentalintervertebral disk herniation in rabbits. J Spinal Disord. 1988. 1(1): 81-5.
[15] Lipson SJ. Metaplastic proliferative fibrocartilage as an alternative concept to herniated intervertebral disc. Spine (Phila Pa 1976). 1988. 13(9): 1055-60.
[16] Sobajima S, Kompel JF, Kim JS, et al. A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology. Spine (Phila Pa 1976). 2005. 30(1): 15-24.
[17] Masuda K, Aota Y, Muehleman C, et al. A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine (Phila Pa 1976). 2005. 30(1): 5-14.
[18] Gruber HE, Johnson TL, Leslie K, et al. Autologous intervertebral disc cell implantation: a model using Psammomys obesus, the sand rat. Spine (Phila Pa 1976). 2002. 27(15): 1626-33.
[19] Olmarker K, Blomquist J, Stromberg J, Nannmark U, Thomsen P, Rydevik B. Inflammatogenic properties of nucleus pulposus. Spine (Phila Pa 1976). 1995. 20(6): 665-9.
[20] Satoh K, Konno S, Nishiyama K, Olmarker K, Kikuchi S. Presence and distribution of antigen-antibody complexes in the herniated nucleus pulposus. Spine (Phila Pa 1976). 1999. 24(19): 1980-4.
[21]姜为民,杨惠林.退变腰椎间盘组织的血管浸润现象及其意义.中华骨科杂志. 1998. (09): 24-26.
[22] BmWn T.Some mechanieal test on lumbo-sacral spine with particalar reference to the intervertebral disc:a preliminary report.Joint Srug,1957{39A:l135
[23] Adams MA,Hutt0n WC.The relevance of torsion to the mechenical derangemengt of the lumbar.Spine,1981 I6:241
[24] Hansson T.Bengt R.The relation between mineral compression fractures,and disc degeneration in lumbar vertebrace.Spine,1981;6:147
[25] Hunter C J.The notochordal cell in the nucleus pulposus:a review in the context oftissue engineering.Tissue Engineering,2003
[26] Haefeli M,Kalberer F,Saegesser D,et al Spine.2006:31(14):1522-1531;
[27] Freemont AJ.1e Maitre CL .Watkins A,et al.Expert Rev Mol Med.200l;2001:1-10.
[28] Gruber HE.Norton HJ.Ingram JA,et al.Spine,2005;30(6):625-630.
[29] Paul R.Haydon RC,Cheng H.et al.Spine.2003;28(8):755-763.
[30] Sekiya I.Tsuji K.Koopman P.et al.J Biol Chem.2000;275(15):10738-10744.
[31] Lotz M. CIin Orthop.200l;391(suppl):S108-S115.
[32] Kim KS.Yoon ST.Park JS.et al.J Neurosurg.2003;99(3 Suppl):291-297.
[33] Roughley P,Martens D.Rantakokko J.et al.Eur Cell Mater.2006:11:l-7.
[34] Omlor GW.Lorenz H.Engelleiter K.et al.J Orthop Res.2006:24(3):385-392.
[35] SilberbergR,Aufdermaur M, Adler JH.Degeneration of the intervertebral disksand spondylosis in aging sand rats. Arch Pathol Lab Med 1979;103(5):231–5.
[36] Adler JH, Schoenbaum M, Silberberg R. Early onset of disk degeneration and spondylosis in sand rats (Psammomys obesus). Vet Pathol 1983;20:13–22.
[37] Moskowitz RW, Ziv I, Denko CW, Boja B, Jones PK, Adler JH.Spondylosis in sand rats: a model of intervertebral disc degeneration and hyperostosis. J Orthop Res 1990;8:401–11.
[38] Ziv I, Moskowitz RW, Kraise I, Adler JH,Maroudas A. Physicochemical properties of the aging and diabetic sand rat intervertebral disc.J Orthop Res 1992;10:205–10.
[39] Ziran BH, Pineda S, Pokharna H, Esteki A, Mansour JM, Moskowitz RW. Biomechanical, radiologic, and histopathologic correlations in the pathogenesis of experimental intervertebral disc disease. Spine1994;19:2159–63.
[40] Gruber HE, Johnson T, Norton HJ, Hanley EN Jr. The sand rat model for disc degeneration: radiologic characterization of age-related changes: cross-sectional and prospective analyses. Spine 2002;27:230–4.
[41] Gruber HE, Johnson TL, Leslie K, et al. Autologous intervertebral disc cell implantation: a model using Psammomys obesus, the sand rat. Spine2002;27:1626–33.
[42] Berry R. Genetically controlled degeneration of the nucleus pulposus in the mouse. J Bone Joint Surg 1961;43B:387–93.
[43] Silberberg R, Gerritsen G. Aging changes in intervertebral discs and spondylosis in Chinese hamsters. Diabetes 1976;25:477–83.
[44] Cole TC, Ghosh P, Taylor TK. Variations of the proteoglycans of the canine intervertebral disc with ageing. Biochim Biophys Acta 1986;880:209–19.
[45] Goggin JE, Li AS, Franti CE. Canine intervertebral disk disease:characterization by age, sex, breed, and anatomic site of involvement.Am J Vet Res 1970;31:1687–92.
[46] Ghosh P, Taylor TK, Braund KG, Larsen LH. The collagenous and non-collagenous protein of the canine intervertebral disc and their variation with age, spinal level and breed. Gerontology 1976;22:124–34.
[47] Gillett NA, Gerlach R, Cassidy JJ, Brown SA. Age-related changes in the beagle spine. Acta Orthop Scand 1988;59:503–7.
[48] Lauerman WC, Platenberg RC, Cain JE, Deeney VF. Age-related disk degeneration: preliminary report of a naturally occurring baboon model. J Spinal Disord 1992;5:170–4.
[49] Goff C, Landmesser W. Bipedal rats and mice: laboratory animals for orthopaedic research. J Bone Joint Surg 1957;39A:616–22.
[50] Yamada K. The dynamics of experimental posture. Experimental study of intervertebral disk herniation in bipedal animals. Clin Orthop 1962;25:20–31.
[51] Higuchi M, Abe K, Kaneda K. Changes in the nucleus pulposus of the intervertebral disc in bipedal mice. A light and electron microscopic study. Clin Orthop 1983;175:251–7.
[52] Cassidy JD, Yong-Hing K, Kirkaldy-Willis WH, Wilkinson AA. A study of the effects of bipedism and upright posture on the lumbosacral spine and paravertebral muscles of the Wistar rat. Spine 1988;13:301–8.
[53] Hutton WC, Yoon ST, Elmer WA, et al. Effect of tail suspension (or simulatedweightlessness) on the lumbar intervertebral disc: study of proteoglycans and collagen. Spine 2002;27:1286–90.
[54] Lotz J, Colliou O, Chin J, Duncan N, Liebenberg E. Compressioninduced degeneration of the intervertebral disc: an in vivo mouse model and finite element study. Spine 1998;23:2493–506.
[55] Iatridis JC, Mente PL, Stokes IA, Aronsson DD, Alini M. Compression-induced changes in intervertebral disc properties in a rat tail model. Spine 1999;24:996–1002.
[56] Ching CT, Chow DH, Yao FY, Holmes AD. The effect of cyclic compression on the mechanical properties of the inter-vertebral disc:an in vivo study in a rat tail model. Clin Biomech (Bristol, Avon)2003;18:182–9.
[57] Kroeber MW, Unglaub F, Wang H, et al. New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration. Spine 2002;27:2684–90.
[58] Hadjipavlou AG, Simmons JW, Yang JP, Bi LX, Simmons DJ,Necessary JT. Torsional injury resulting in disc degeneration in the rabbit: II. Associative changes in dorsal root ganglion and spinal cord neurotransmitter production. J Spinal Disord 1998;11:318–21.
[59] Hadjipavlou AG, Simmons JW, Yang JP, et al. Torsional injury resulting in disc degeneration: I. An in vivo rabbit model. J Spinal Disord 1998;11:312–7.
[60] Miyamoto S, Yonenobu K, Ono K. Experimental cervical spondylosis in the mouse. Spine 1991;16(10 suppl):S495–500.
[61] Sullivan J, Farfan H, Kahn D. Pathologic changes with intervertebral joint rotational instability in the rabbit. Can J Surg 1971;14:71–9.
[62] Phillips FM, Reuben J, Wetzel FT. Intervertebral disc degeneration adjacent to a lumbar fusion. An experimental rabbit model. J Bone Joint Surg Br 2002;84:289–94.
[63] Keyes D, Compere E. The normal and pathological physiology of the nucleus pulposus of the intervertebral disc: an anatomical, clinical,and experimental study. J Bone Joint Surg 1932;14:897–938.
[64] Smith J, Walmsley R. Experimental incision of the intervertebral disc. J Bone Joint Surg 1951;33B:612–25.
[65] Haimovici EH. Experimental disc lesion in rabbits. The effect of repeated ACTH administration. Acta Orthop Scand 1970;41:505–21.
[66] Lipson SJ, Muir H. Experimental intervertebral disc degeneration:morphologic and proteoglycan changes over time. Arthritis Rheum1981;24:12–21.
[67] Urayama S. Histological and ultrastructural study of degeneration of the lumbar intervertebral disc in the rabbit following nucleotomy,with special reference to the topographical distribution pattern of the degeneration. Nippon Seikeigeka Gakkai Zasshi 1986;60:649–62.
[68] Masuda K, Aota Y, Muehleman C, et al. A novel rabbit model of mild, reproducible disc degeneration by an annulus needle puncture:correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine 2005;30:5–14.
[69] Aota Y, Masuda K, Nguyen C, Andersson G, Thonar EJ, An H.Radiological and MRI analyses of a novel rabbit model: A mild,progressive disc degeneration. Ortho Res Soc Trans 2002;27(abstr.):118.
[70] Muehleman C, Masuda K, Imai Y, et al. Histological assessment of a novel needle puncture model: a mild, progressive intervertebral disc degeneration. Ortho Res Soc Trans 2003;28(abstr.):86.
[71] Kompel J, Sobajima S, Clarke C, et al. MRI and histological analysis of a rabbit model of disc degeneration. Ortho Res Soc Trans 2003;28:253.
[72] Osti OL, Vernon-Roberts B, Fraser RD. 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model. Spine 1990;15:762–7.
[73] Kaapa E, Holm S, Han X, Takala T, Kovanen V, Vanharanta H.Collagens in the injured porcine intervertebral disc. J Orthop Res 1994;12:93–102.
[74] Kaapa E, Zhang LQ, Muona P, Holm S, Vanharanta H, Peltonen J.Expression of type I,III, and VI collagen mRNAs in experimentally injured porcine intervertebral disc. Connect Tissue Res 1994;30:203–14.
[75] Kaapa E, Gronblad M, Holm S, Liesi P, Murtomaki S, Vanharanta H.Neural elements in the normal and experimentally injured porcine intervertebral disk. Eur Spine J 1994;3:137–42.
[76] Pfeiffer M, Griss P, Franke P. Degeneration model of the porcine lumbar motion segment: effects of various intradiscal procedures. Eur Spine J 1994;3:8–16.
[77] Holm S, Holm AK, Ekstrom L, Karladani A, Hansson T. Experimental disc degeneration due to endplate injury. J Spinal Disord Tech 2004;17:64–71.
[78] Wada E, Ebara S, Saito S, OnoK. Experimental spondylosis in the rabbit spine. Overuse could accelerate the spondylosis. Spine 1992;17(3suppl):S1–6.
[79] Bradford DS, Cooper KM, Oegema TR Jr. Chymopapain, chemonucleolysis,and nucleus pulposus regeneration. J Bone Joint Surg Am 1983;65:1220–31.
[80] Bradford DS, Oegema TR Jr, Cooper KM, Wakano K, Chao EY.Chymopapain, chemonucleolysis, and nucleus pulposus regeneration.A biochemical and biomechanical study. Spine 1984;9:135–47.
[81] Kahanovitz N, Arnoczky SP, Kummer F. The comparative biomechanical,histologic, and radiographic analysis of canine lumbar discs treated by surgical excision or chemonucleolysis. Spine 1985;10:178–83.
[82] Spencer DL, Miller JA, Schultz AB. The effects of chemonucleolysis on the mechanical properties of the canine lumbar disc. Spine 1985;10:555–61.
[83] Nitobe T, Harata S, Okamoto Y, Nakamura T, Endo M. Degradation and biosynthesis of proteoglycans in the nucleus pulposus of canine intervertebral disc after chymopapain treatment. Spine 1988;13:1332–9.
[84] Takahashi T, Nakayama M, Chimura S, et al. Treatment of canine intervertebral disc displacement with chondroitinase ABC. Spine 1997;22:1435–9; discussion 46–7.
[85] Ono A, Harata S, Takagaki K, Endo M. Proteoglycans in the nucleus pulposus of canine intervertebral discs after chondroitinase ABC treatment.J Spinal Disord1998;11:253–60.
[86] Zook BC, Kobrine AI. Effects of collagenase and chymopapain on spinal nerves and intervertebral discs of cynomolgus monkeys. J Neurosurg 1986;64:474–83.
[87] Olmarker K, Rydevik B, Dahlin LB, Danielsen N, Nordborg C. Effects of epidural and intrathecal application of collagenase in the lumbar spine: an experimental study in rabbits. Spine 1987;12:477–82.
[88] Kato F, Iwata H, Mimatsu K, Miura T. Experimental chemonucleolysis with chondroitinase ABC. Clin Orthop 1990;301–8.
[89] Eurell JA, Brown MD, Ramos M. The effects of chondroitinase ABC on the rabbit intervertebral disc. A roentgenographic and histologic study. Clin Orthop 1990;256:238–43.
[90] Takahashi T, Kurihara H, Nakajima S, et al. Chemonucleolytic effects of chondroitinase ABCon normal rabbit intervertebral discs. Course of action up to 10 days postinjection and minimum effective dose. Spine 1996;21:2405–11.
[91] Sumida K, Sato K, Aoki M, Matsuyama Y, Iwata H. Serial changes in the rate of proteoglycan synthesis after chemonucleolysis of rabbit intervertebral discs. Spine 1999;24:1066–70.
[92] Takenaka Y, Revel M, Kahan A, Amor B. Experimental model of disc herniations in rats for study of nucleolytic drugs. Spine 1987;12:556–60.
[93] Norcross JP, Lester GE, Weinhold P, Dahners LE. An in vivo model of degenerative disc disease. J Orthop Res 2003;21:183–8.
[94] Sasaki M, Takahashi T, Miyahara K, Hirose AT. Effects of chondroitinase ABC on intradiscal pressure in sheep: an in vivo study. Spine 2001;26:463–8.
[95] Greg Anderson D, Li X, Tannoury T, Beck G, Balian G. A fibronectin fragment stimulates intervertebral disc degeneration in vivo. Spine 2003;28:2338–45.
[96] Oda H, Matsuzaki H, Tokuhashi Y, Wakabayashi K, Uematsu Y,Iwahashi M. Degeneration of intervertebral discs due to smoking:experimental assessment in a rat-smoking model. J Orthop Sci 2004;9:135–41.
[97] Iwahashi M, Matsuzaki H, Tokuhashi Y, Wakabayashi K, Uematsu Y.Mechanism of intervertebral disc degeneration caused by nicotine in rabbits to explicate intervertebral disc disorders caused by smoking.Spine 2002;27:1396–401.
[1] Humzah, M.D., and Soames, R.W. Human intervertebral disc: Structure and function. Anat. Rec. 220, 337, 1988.
[2] Holm, S.H. Nutritional and pathophysiologic aspects of the lumbar intervertebral disc. In: Wiesel, S.W., Weinstein, J.N., Herkowitz, H.N., Dvorak, J., and Bell, G.R., eds. The Lumbar Spine. Philadelphia, PA: W.B. Saunders, 1996, pp.285–310.
[3] DePalma, A.F., and Rothman, R.H. The Intervertebral Disc. Philadelphia, PA: W.B. Saunders, 1970.
[4] Iatridis, J.C., Weidenbaum, M., Setton, L.A., and Mow,V.C. Is the nucleus pulposus a solid or a fluid? Mechanical behaviors of the nucleus pulposus of the human intervertebral disc. Spine 21, 1174, 1996.
[5] Roberts, S., Menage, J., Duance, V., Wotton, S., and Ayad, S. Collagen types aroundthe cells of the intervertebral disc and cartilage end plate: An immunolocalization study. 1991 Volvo Award in Basic Sciences. Spine 16, 1030, 1991.
[6] Sztrolovics, R., Alini, M., Mort, J.S., and Roughley, P.J.
[7] Age-related changes in fibromodulin and lumican in human intervertebral discs. Spine 24, 1765, 1999.
[8] Melrose, J., Ghosh, P., and Taylor, T.K. A comparative analysis of the differential spatial and temporal distributions of the large (aggrecan, versican) and small (decorin, biglycan, fibromodulin) proteoglycans of the intervertebral disc. J. Anat. 198, 3, 2001.
[9] Trout, J.J., Buckwalter, J.A., Moore, K.C., and Landas,S.K. Ultrastructure of the human intervertebral disc. I.Changes in notochordal cells with age. Tissue Cell 14, 359,1982.
[10] Trout, J.J., Buckwalter, J.A., and Moore, K.C. Ultrastructure of the human intervertebral disc. II. Cells of the nucleus pulposus. Anat. Rec. 204, 307, 1982.
[11] Maldonado, B.A., and Oegema, T.R.J. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J. Orthop. Res. 10, 677, 1992
[12] Trout, J.J., Buckwalter, J.A., Moore, K.C., and Landas,S.K. Ultrastructure of the human intervertebral disc. I.Changes in notochordal cells with age. Tissue Cell 14, 359,1982.
[13] Trout, J.J., Buckwalter, J.A., and Moore, K.C. Ultrastructure of the human intervertebral disc. II. Cells of the nucleus pulposus. Anat. Rec. 204, 307, 1982.
[14] Stevens, J.W., Kurriger, G.L., Carter, A.S., and Maynard,J.A. CD44 expression in the developing and growing rat intervertebral disc. Dev. Dyn. 219, 381, 2000.
[15] Maldonado, B.A., and Oegema, T.R.J. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J. Orthop. Res. 10, 677, 1992.
[16] Fowlis, D., Colnot, C., Ripoche, M.A., and Poirier, F.Galectin-3 is expressed in the notochord, developing bones,and skin of the postimplantation mouse embryo. Dev. Dyn.203, 241, 1995.
[17] Domowicz, M., Li, H., Hennig, A., Henry, J., Vertel, B.M.and Schwartz, N.B. Thebiochemically and immunologically distinct CSPG of notochord is a product of the aggrecan gene. Dev. Biol. 171, 655,1995.
[18] Oganesian, A., Zhu, Y., and Sandell, L.J. Type IIA procollagen amino propeptide is localized in human embryonic tissues. J. Histochem. Cytochem. 45, 1469, 1997.
[19] Zhu, Y., McAlinden, A., and Sandell, L.J. Type IIA procollagen in development of the human intervertebral disc: Regulated expression of the NH2-propeptide by enzymic processing reveals a unique developmental pathway. Dev.Dyn. 220, 350, 2001.
[20] Brissett, N.C., and Perkins, S.J. The protein fold of the hyaluronate-binding proteoglycan tandem repeat domain of link protein, aggrecan and CD44 is similar to that of the C-type lectin superfamily. FEBS Lett. 388, 211, 1996.
[21] Watanabe, H., Cheung, S.C., Itano, N., Kimata, K., and Yamada,Y. Identification of hyaluronan-binding domains of aggrecan. J. Biol. Chem. 272, 28057, 1997.
[22] Hardingham, T.E., Fosang, A.J., and Dudhia, J. The structure, function and turnover of aggrecan, the large aggregating proteoglycan from cartilage. Eur. J. Clin. Chem. Clin. Biochem. 32, 249, 1994.
[23] Dong, S., and Hughes, R.C. Macrophage surface glycoproteins binding to galectin-3 (Mac-2-antigen). Glycoconj. J. 14, 267, 1997.
[24] Kuwabara, I., and Liu, F.T. Galectin-3 promotes adhesion of human neutrophils to laminin. J.Immunol. 156, 3939,1996.
[25] Sato, S., and Hughes, R.C. Binding specificity of a baby hamster kidney lectin for H type I and II chains, polylactosamine glycans, and appropriately glycosylated forms of laminin and fibronectin. J. Biol. Chem. 267,6983, 1992.
[26] Probstmeier, R., Montag, D., and Schachner, M. Galectin-3, a b-galactoside-binding animal lectin, binds to neural recognition molecules. J. Neurochem. 64, 2465, 1995.
[27] Hayes, A.J., Benjamin, M., and Ralphs, J.R. Role of actin stress fibres in the development of the intervertebral disc: Cytoskeletal control of extracellular matrix assembly. Dev.Dyn. 215, 179, 1999.
[28] Domowicz, M., Li, H., Hennig, A., Henry, J., Vertel, B.M.and Schwartz, N.B. Thebiochemically and immunologically distinct CSPG of notochord is a product of the aggrecan gene. Dev. Biol. 171, 655, 1995.
[1]Ogata K, Kur ki P , Celis J E , et al . Monoclonal a ntibodies to a nuclea r p rotein ( PCNA/ Cyclin) associated wit h DNA replication[J ] . Exp Cell Res ,1987 ,168 (2) :475 - 486.
[2] Van Dierendonck J H, Wijsman J H, Keijzer R , et al . Cell2cycle2related staining patterns of anti2proliferating cell nuclear antigen monoclonal antibodies. Comparison with BrdUrd labelling and Ki267 staining[J ] . Am J Pathol ,1991 ,138(5) :1165 - 1172.
[3] Takashi Tsuji, Kazuhiro Chiba, Hideaki Imabayashi, etc. Age-Related Changes in Expression of Tissue Inhibitor of Metalloproteinases-3 Associated With Transition From the Notochordal Nucleus Pulposus to the Fibrocartilaginous Nucleus Pulposus in Rabbit Intervertebral Disc. SPINE , 32(8), pp 849–856
[4] Christopher J. Hunter, John R. Matyas, Neil A. Duncan. Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus: a species comparison J. Anat. 2004,205, pp357–362.
[5] Pulposus Rodolfo Cappello, Joseph L. E. Bird, Dirk Pfeiffe, Notochordal CellProduce and Assemble Extracellular Matrix in a Distinct Manner, Which May Be Responsible for the Maintenance of Healthy Nucleus r. spine , 2006, 31(8), pp 873–882
[6]Christopher J. Hunter,John R. Matyas, Neil A. Duncan. The three-dimensional architecture of the notochordal nucleus pulposus: novel observations on cell structures in the canine intervertebral disc. J. Anat. 2003,202, pp279D291
[7] Horwitz, T. The human notochord: A study of its development and regression, variations, and pathologic derivative, chordoma. Indianapolis: 1977.
[8] Horwitz, T. The human notochord: A study of its development and regression, variations, and pathologic derivative, chordoma. Indianapolis: 1977.
[9] Maldonado, B.A., and Oegema, T.R.J. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J. Orthop. Res. 1992, 10, 677.
[10] Aguiar, D.J., Johnson, S.L., and Oegema, T.R. Notochordal cells interact with nucleus pulposus cells: Regulation of proteoglycan synthesis. Exp. Cell Res. 1999,.246, 129.
[11] Maldonado, B.A., and Oegema, T.R.J. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J. Orthop. Res. 1992 ,10, 677.
[12] Biochemical Society Transactions (2002) Volume 30, part 6 839-844 The role of disc cell heterogeneity in determining disc biochemistry: a speculation T. R. Oegema, Jr1
[13] Aguiar, D.J., Johnson, S.L., and Oegema, T.R. Notochordal cells interact with nucleus pulposus cells: Regulation of proteoglycan synthesis. Exp. Cell Res. 1999.246, 129.
[14] Adler JH, Schoenbaum M, Silberberg R(1983) Early onset of disk degeneration and spondylosis in sand rats (Psammomys obesus).Vet.Pathol.20, 13–22.
[15] Aguiar DJ, Johnson SL, Oegema TR(1999) Notochordal cells interact with nucleus pulposus cells: regulation of proteoglycan synthesis.Exp.Cell Res.246, 129–137.
[16] Anderson DG, Izzo MW, Hall DJ, et al.(2002) Comparative gene expression profiling of normal and degenerative discs:analysis of a rabbit annular laceration model.Spine.27,1291–1296.
[17] Ariga K, Miyamoto S, Nakase T, et al.(2001) The relationship between apoptosis ofendplate chondrocytes and aging and degeneration of the intervertebral disc.Spine.26, 2414–2420.
[18] Bell GR(1996) Anatomy of the lumbar spine: developmental to normal adult anatomy. In The Lumbar Spine(eds WieselSW, Weinstein JN, Herkowitz HN, Dvorak J, Bell GR), pp. 43–52.
[19] Bray JP, Burbidge HM(1998) The canine intervertebral disk.Part Two: Degenerative changes– nonchondrodystrophoid versus chondrodystrophoid disks.J.Am.Anim Hosp.Assoc.34, 135–144.
[20] Butler WF(1989) Comparative anatomy and development of the mammalian disc. In The Biology of the Intervertebral Disc(ed. Gosh P), pp. 84–108. Boca Raton: CRC Press.
[21] DePalma AF,Rothman RH(1970)The Intervertebral Disc, 1stedn. Philadelphia, PA: W.B. Saunders Company.
[22] Errington RJ, Puustjarvi K, White IR, Roberts S, Urban JP(1998)Characterisation of cytoplasm-filled processes in cells of the intervertebral disc.J.Anat.192, 369–378.
[23] Frick SL, Hanley EN, Meyer RA, JrRamp WK, JrChapmanTM(1994) Lumbar intervertebral disc transfer. A canine study.Spine19, 1826–1834.
[24] Ganey T, Libera J, Moos V, et al.(2003) Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc.Spine.28, 2609–2620.
[25] Hansen HJ(1952) A pathologic–anatomical study on disc degeneration in dog.Acta Orthop.Scand Suppl.11.
[26] Hansen HJ(1959) Comparative views on the pathology of disk degeneration in animals.Lab.Invest.8, 1242–1265.
[27] Hayes AJ, Benjamin M, Ralphs JR(2001) Extracellular matrix indevelopment of the intervertebral disc.Matrix Biol.20, 107–121.
[28] Holm SH(1996) Nutritional and pathophysiologic aspects of the lumbar intervertebral disc. In The Lumbar Spine(edsWiesel SW, Weinstein JN, Herkowitz HN, Dvorak J, Bell GR),pp. 285–310. philadelphia, PA: W.B. Saunders Company.
[1] Lob A, Holm C. Dic zusammenhange zwisehen den verletzungen der bandscheiben and der spondylosis deformans im tierversuch. Dtsch Ztschr Chr, 1933, 240:421-440.
[2] Key JA, Ford LT. Experimental intervertebral-disc lesions. J Bone Joint Surg(Am),1948, 30:621-629.
[3] Hansen HJ. A pathologic-anatomical study on disc degeneration in dogs. Acta Orthop Scand(Br),1952, 11(suppl 3):111-117.
[4] Berry RJ. Genetically controlled degeneration of the nucleus pulposus in the mouse. J Bone Joint Surg(Br), 1961, 43:387-393.
[5] Gillett NA,Gerlach R,Cassidy JJ,et a1.Age-related changes in the beagle spine[J].Acta Orthop Scand,1988,59:503-507.
[6] Silberberg R, Aufdermaur M, Adler JH.Degeneration of the intervetebral disks and spondylosis in aging sand rats. Arch Pathol Lab Med, 1979, 103:231 -235.
[7] Osti OL, Vernon -Roberts B, Fraser RD, et al. 1990 Volvo Award in experimenta studys. Anulus tears and intervertebral disdegeneration:an experimental study using an animal model. Spine, 1990, 15:762-767.
[8] Nguyen CM, Haughton VM, Ho KC, et al. A model for studying intervertebral disc degeneration with magnetic resonace and a nucletome. Invest Radiol, 1989, 24:407-409.
[9] Lipson SJ, Muir H. Proteoglycans in experimental intervertebral disc degeneration. Spine, 1981, 6:194-210.
[10] Keyes DC, Compere EL. The normal and pathological physiolgy of the nucleus pulposus of the intervertebral disc:an anatomical,clinical, and experimental study. J Bone Joint Surg(Br), 1932, 14:897 -938.
[11] Bercovici S, Paraschivesco E. Recherche experimentale sur ladiscopathie vertebrale degenerative. Rev Rheum, 1958, 25:487 -499.
[12] Lu DS,Luk KD,Lu W,et a1.Spinal flexibility in ovease after chymopapain injectionis dose dependent:a possible alteract to antervior release in sodisis [J].Spine,2004,29:123-128
[13] Norcross JP,Lester GE,Weinhdd,et a1.An in vivo model of degenerative disc disease[J].J Orthop Res,2003,21:183—188.
[14] Greg-Anderson D. A fibronectin fragment stimulates intervertebral disc degeneration in vivo[J].Spine,2003,28:2338—2345.
[15] Cassidy JD , Yong-Hing K, Kirkaldy- Willis WH, et al. A study of the effects bipedism and upright posture on the lumbosacral spine and paravertebral muscles of the Wistar rat. Spine, 1988, 13:301 -308.
[16] Sullivan JD, Farfan HF, Kahn DS. Pathologic changes with intervertebral joint rotational instability in the rabbit. Can J Surg, 1971,14:71 -79.
[17] Lindblom K. Intervertebral -disc degeneration considered as a pressure atrophy . J Bone Joint Surg(Am), 1957, 39:933 -945.
[18] Wada E, Ebara S, Saito S, et al. Experiment spondylosis in the rabbit spine:overuse could accelerate the spondylosis. Spine, 1992, 17(suppl 3):1 -6.
[19] Schendel MJ, Dekutoski MB, Ogilvie JW,et al. Kinematics of the canine lumbar intervertebral joint:an in vivo study before and after adjacent instrumentation. Spine, 1995,20:2555 -2564.
[20] Cole TC, Burkhardt D, Ghosh P, et al. Effects of spinal fusion on the proteoglycans of the canine intervertebral disc. J Orthop Res,1985, 3:277 -291.
[21] Oda H,Matsuzaki H,Tokuhashi Y,et a1.Degeneration of intervertebral discs due to smoking:experimental assessment in a rat-smoking model[J].J Orthop Sci,2004,9(2):135—141.
[22] Wang T,Zhang L,Huang C,et a1.Relationship between osteopenia and lumbar intervcrtebral disc degeneration in ovariectomized rats[J].Calcif Tissue I nt,2004,75(3):205—213.
[23] Haefeli M,Kalberer F,Saegesser D,et al Spine.2006:31(14):1522-1531;
[24] Freemont AJ.1e Maitre CL .Watkins A,et al.Expert Rev Mol Med.200l;2001:1-10.
[25] Weiler C,Nerlich AG,Bachmeier BE.et al.Spine.2005;30(1):44-53.
[26] le Maitre CL, Freemont AJ, Hoyland JA. Arthritis Res Ther.2005:7(4):R732-R745]
[27] le Maitre CL, Freemont AJ, Hoyland JA. Int J Exp Pathol, 2006,87(1):17-28.
[28] Maeda S, Kokubun S. Spine,2000;25(2):166-169.
[29] Specchia N.Pagnotta A,Toesca A.et al.Eur Spine J.2002;11(2):145-151.
[30] Moroney P.Waston RWG.Burke JG.et al.PH and inflammatory mediators modulate nucleus puposus cytokine secretion.12th Annual Metting of European Orthopedic Research Society.Lausanne,Switzerland,2002:1-32.
[31] Rannou F.Corvol MT.Hudry C.et al.Spine,2000;25(1):l 7-23.
[32] Shen B,Melrose J.Ghosh P,et al.Eur Spine J.2003;12(1):66-75.
[33] Liu GZ.Ishihara H.Osada R.et al.Spine,200l:26(2):134-141.
[34] Kohyama K.Saura R.Doita M,et al.Kobe J Med Sci.2000;46(6):283-295.
[35] Haro H, Crawford HC, Fingleton B,et al. Matrix metallop roteinase-3-dependent generation of a macrophage chemoattractant in model of hermiated disc resorption[ J ]. J Clin Invest, 2000, 105 (2) : 133-141.
[36] Wallach CJ, Sobajima S,Watanabe Y, et al. Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs[ J ]. Spine, 2003, 28 (20) : 2331-2337.
[37] Le Maitre CL. Freemont AJ. Hoyland JA. Localization of degradable enzymes and their inhibitors in the degenerate human intervertebral disc[ J ]. J Pathol, 2004, 24 (1) : 47-54.
[38] Nishida T. Kinetics of tissue and serum matrix metalloproteinase-3 and tissue inhibitor of metalloprotiinases-1 in intervetebral disc degeneration and disc hermiation [ J ]. Kurume Med J, 1999, 46 (1) 39-50.
[39] Sobajima S, Shimer AL, Chadderdon RC, et al. Quantitative analysis of gene expression in a rabbit model of intervertebral disc degeneration by real-time polymerase chain reaction [ J ]. Spine, 2005, 5 (1) : 14-23.
[40] Masuda K, Imai Y, Okuma M, et al. Spine,2006;31(7):742-754.
[41] Tolonen J.Gronblad M,Vanharanta H.et al.Eur Spine J.2006;15(5):588-596.
[42] Wa1lach CJ.Gilbertson LG.Kang JD.Spine.2003;28(15 Suppl):S93-S98.
[43] Zhang Y,Li Z.Thonar EJ.et al.Spine.2005;30(23):260l-2607.
[44] Tim-Yoon S.Su-Kim K,Li J.et al,Spine.2003;28(16):1773-1780.
[45] Paassilta P.Lohiniva J,Goring HH.et al.JAMA.2001;285(14):1843-1849.
[46] Jim JJ.Noponen-Hietala N,Cheung KM.et al.Spine.2005;30(24):2735-2742.
[47] Gruber HE.Norton HJ.Ingram JA,et al.Spine,2005;30(6):625-630.
[48] Paul R.Haydon RC,Cheng H.et al.Spine.2003;28(8):755-763.
[49] Sekiya I.Tsuji K.Koopman P.et al.J Biol Chem.2000;275(15):10738-10744.
[50] Lotz M. CIin Orthop.200l;391(suppl):S108-S115.
[51] Kim KS.Yoon ST.Park JS.et al.J Neurosurg.2003;99(3 Suppl):291-297.
[52] Roughley P,Martens D.Rantakokko J.et al.Eur Cell Mater.2006:11:l-7.
[53] Omlor GW.Lorenz H.Engelleiter K.et al.J Orthop Res.2006:24(3):385-392.
[54] Kanemoto M,Hukuda S,Komiya Y,et al. Immunohistochemical study of Matrix Metalloproteinase-3 and Tissue Inhibitor of Metallo proteinase-1 in human intervertebral discs[J]. Spine,1996,21:1-8.
[55] MuIIer-Ladner U,Roberts CR,Franklin BN,et al. Human IL-1 Ra gene transfer into human synovial fibroblasts is chondroprotective[J]. J Immunol. 1997,158:3492—3498.
[56] Bandara G,Mueller GM,Galea-Lauri J,et al. Intraarticular expression of biologically active interleukin 1-receptor-antagonist protein by ex vivo gene transfer[J]. Proc Natl Acad Sci USA,1993,90:10764-10768.
[57] Olmarker K,Rydevik B.Selective inhibition of tumor necrosis factoralpha prevents nucleus pulposus-induced thrombus formation, intraneuraI edema, and reduction of nerve conduction velocity:possible implications for future pharmacologic treatment strategies of sciatica[J]. Spine,2001,26:863-869.
[58] Thompson JP,Oegema TR Jr,Bradford DS.Stimulation of mature canineintervertebral disc by growth factors.Spine,1991,16:253—260.
[59] Okuda S,Myoui A,Ariga K,et a1.Mechanisms of age-related decline in insulin-like growth factor-I dependent proteoglycan synthesis in rat intervertebral disc cells.Spine,2001,26:2421—2426.
[60] Gmber HE,Norton HJ,Hanley EN Jr.Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro.Spine,2000.25:2153—2157.
[61] Matsunaga S,Nagano S,Onishi T,et al. Age-related change in expression of transforming growth factor-beta and receptors in cells of intervertebral discs[J].J Neurosurg Spine,2003,98:63-67.
[62] Nishida K,Kang JD,Gilbertson LG,et al. Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy:an in vivo study of adenovirus-mediated transfer of the human transforming growth factor beta 1 encoding gene[J]. Spine.1999.24:2419—2425.
[63] Tan Y,Hu Y,Tan J.Extracellular matrix synthesis and ultrastructural changes of degenerative disc cells transfected by Ad/CMV—hTGFbeta 1[J]. Chin Med J(Engl),2003,116:1399—1403.
[64] Walsh AJL,Bradford DS,Lotz JCS. In vivo growth factor treatment of degenerated intervertebral discs[J]. Spine,2004,29:156-163.
[65] Yoon ST,Kim K,Li J,et al. The effect of bone morphogenetic protein-2 on rat intervertebral disc cells in vitro[J]. Spine,2003,28:1773-1780.
[66] Kim KS,Yoon ST,Park JS,et al. Inhibition of proteoglycan and type II collagen synthesis of disc nucleus cells by nicotine [J]. Spine,2003,99:291—297.
[67] Kim DJ,Moon SH,Kim H,et a1.Bone morphogenetic protein-2 facilitates expression of chondrogenic,not osteogenic,phenotype of human intervertebral disc cells[J]. Spine,2003,28:2679-2684.
[68] Moon S,Lee H,Park M,et al. BMP-2 upregulates the mRNA expression of aggrecan,collagen type I,and collagen type II in human intervertebral disc cells. in:Transactions of the 48th Annual Meeting of the Orthopaedic Research Society,Vol27,Dallas.TX.February 10-13, 2002.
[69] Takegami K,Thonar EJ,An HS,et a1.Osteogenic protein一1 enhances matrix replenishment by intervertebral disc cells previously exposed to interleukin一1.Spine,2002,27:1318—1325.
[70] ZhangY,An HS,Song S,et a1.Growthfactor osteogenic protein一1:differing effects on cells fromthree distinct zones in the bovine intervertebral disc.Am J Phys Med Rehabil,2004,83:515—521.
[71] Chang SC,Hoang B,Thomas JT,et a1.Cartilage—derived morphogenetic proteins . New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development.J Biol Chem,1994,269:28227—28234.
[72] Li J,Kim KS,Park JS,et a1.BMP一2 and CDMP一2:stimulation of chondrocyte production of proteoglycan.J Orthop Sci,2003,8:829—835.
[73] Walsh AJL,Bradford DS,Lotz JCS. In vivo growth factor treatment of degenerated intervertebral discs[J]. Spine,2004,29:156-163.
[74] Wang H,Kroeber M,Hanke M,et al. Release of active and depot GDF-5 after adenovirus-mediated overexpression stimulates rabbit and human intervertebral disc cells[J].J Mol Med.2004.82:126—134.
[75] Mwale F,Demers CN,Petit A,et a1.A synthetic peptide of link protein stimulates the biosynthesis of collagens II,IX and proteoglyean by cells of the intervertebral disc.J Cell Bioehem,2003,88:1202一l213.
[76]Yoon ST,Kim K,Li J,et al. The effect of bone morphogenetic protein-2 on rat intervertebral disc cells in vitro[J]. Spine,2003,28:1773-1780.
[77] Paul R,Haydon RC,Cheng H,et al. Potential use of sox9 gene therapy for intervertebral degenerative disc disease[J]. Spine,2003.28:755—763.
[78] Israel DI,Nove J,Kems KM et a1.Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo.Growth Factors,1996,13:291—300.
[1] Kim KW, Lim TH, Kim JG, Jeong ST, Masuda K, An HS. 2003. The origin of chondrocytes in the nucleus pulposus and histologic findings associated with the transition of a notochordal nucleus pulposus to a fibrocartilaginous nucleus pulposus in intact rabbit intervertebral discs. Spine 28:982–990.
[2] Kuro-o M, Matsumura Y, Aizawa H,Kawaguchi H, Suga T, Utsugi T,Ohyama Y, Kurabayashi M,Kaname T,Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI.1997. Mutation of the mouse klotho gene leads to a syndrome resembling ageing.Nature 390:45–51.
[3] Maldonado BA, Oegema TR, Jr. 1992. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J Orthop Res 10:677-690.
[4] Humzah, M.D., and Soames, R.W. Human intervertebral disc: Structure and function. Anat. Rec. 220, 337, 1988.
[5] Holm, S.H. Nutritional and pathophysiologic aspects of the lumbar intervertebral disc. In: Wiesel, S.W., Weinstein,J.N., Herkowitz, H.N., Dvorak, J., and Bell, G.R., eds. The Lumbar Spine. Philadelphia, PA: W.B. Saunders, 1996, pp.285–310.
[6] DePalma, A.F., and Rothman, R.H. The Intervertebral Disc.Philadelphia, PA: W.B. Saunders, 1970.
[7] Iatridis, J.C., Weidenbaum, M., Setton, L.A., and Mow,V.C. Is the nucleus pulposus asolid or a fluid? Mechanical behaviors of the nucleus pulposus of the human intervertebral disc. Spine 21, 1174, 1996.
[8] Roberts, S., Menage, J., Duance, V., Wotton, S., and Ayad,S. Collagen types around the cells of the intervertebral disc and cartilage end plate: An immunolocalization study. 1991 Volvo Award in Basic Sciences. Spine 16, 1030, 1991.
[9] Sztrolovics, R., Alini, M., Mort, J.S., and Roughley, P.J.Age-related changes in fibromodulin and lumican in human intervertebral discs. Spine 24, 1765, 1999.
[10] Melrose, J., Ghosh, P., and Taylor, T.K. A comparative analysis of the differential spatial and temporal distributions of the large (aggrecan, versican) and small (decorin,biglycan, fibromodulin) proteoglycans of the intervertebral disc. J. Anat. 198, 3, 2001.
[11] Trout, J.J., Buckwalter, J.A., Moore, K.C., and Landas,S.K. Ultrastructure of the human intervertebral disc. I.Changes in notochordal cells with age. Tissue Cell 14, 359,1982.
[12] Trout, J.J., Buckwalter, J.A., and Moore, K.C. Ultrastructure of the human intervertebral disc. II. Cells of the nucleus pulposus. Anat. Rec. 204, 307, 1982.
[13] Videman, T., and Battie, M.C. Epidemiology of disc disease.In: Wiesel, S.W., Weinstein, J.N., Herkowitz, H.N.,Dvorak, J., and Bell, G.R., eds. The Lumbar Spine. Philadelphia,PA: W.B. Saunders, 1996, pp. 16–27.
[14] Andersson, G.B. The epidemiology of spinal disorders. In:Frymoyer, J.W., ed. The Adult Spine. Philadelphia, PA:Lippincott, 1997.
[15] Frymoyer, J.W. Magnitude of the problem. In: Wiesel,S.W., Weinstein, J.N.,Herkowitz, H.N., Dvorak, J., and Bell, G.R., eds. The Lumbar Spine. Philadelphia, PA: W.B.Saunders, 1996, pp. 8–15.
[16] Pope, M.H. Occupational hazards for low back pain. In:Frymoyer, J.W., ed. The Adult Spine. Philadelphia, PA:Lippincott, 1997.
[17] Wang WL,Abramson JH,Ganguly A,et a1.The surgical pathology of notochordal remnants in adult intervertebral disks:a report of 3 cases[J].Am J Surg Pathol,2008,32 (8)l123-l129.
[18] Le Maitre CL,Freemont AJ,Hoyland JA.Accelerated cellular senescence in degenerate intervertebral discs:a possible role in the pathogenesis of intervertebral disc degeneration l J1.Arthritis Res Ther.2007,9(3):R45.
[19] Hunter CJ,Matyas JR,Duncan NA.The functional significance of cell clusters in the notochordal nucleus pulposus:survival and signaling in the canine intervertebral disc[J[.Spine,2004,29(10):1099～l104.
[20] Hunter CJ,Bianchi S,Cheng P,et a1.Osmoregulatory function of large vacuoles found in notochordal cells of the intervertebral disc running title:an osmoregulatory vacuole lJJ.Mol Cell Biomeeh,2007,4(4):227—237.
[21] Aguiar DJ,Johnson SL,Oegema TR.Notochordal cells interact with nucleus pulposus cells:regulation of proteoglycan synthesis[J].Exp Cell Res,1999,246(1):129—137.
[22] Chen J, Yan W ,Setton LA.Molecular phenotypes of notochordal cells purified from immature nucleus pulposus fJ.Eur Spine J,2006,15(Suppl 3):$303-311.
[23] Oguz E,Tsai TI",Di Martino A,et a1.Galectin-3 expression in the intervertebral disc:a useful marker of the notochord phenotype[J]?Spine,2007,32(1):9-16.
[24] Hunter CJ , Matyas JR , Duncan NA . Cytomorphology of notochordal and chondrocytic cells from the nucleus pulposus:a species comparison[J].J Anat,2004,205(5):357-362.
[25] Hunter CJ,Matyas JR,Duncan NA.The three—dimensional architeeture of the notoehordal nucleus pulposus:novel observations on cell structures in the canine intervertebral disc]J].J Anat,20o3,202(Pt 3):279—291.
[26] Guehring T,Urban JP,Cui Z, et a1.Noninvasive 3D vital imaging and characterization of notochordal cells of the intervertebral disc by femtoseeond near——infrared two——photon laser scanning microscopy and spatial—volume rendering[J].Mierosc Res Teeh,2008,71(4):298—304.
[27]赵献峰,刘浩,丰干均,等.脊索细胞促进髓核软骨样细胞增殖及表型维持Ⅲ.中国修复重建外科杂志,2008,22 (8):939～943.
[28] Aguiar DJ,Johnson SL,Oegema TR.Notochordal cells interactwith nucleus pulposus cells:regulation of proteoglyean synthesis[J].Exp Cell Res,1999,246(1):129-137.
[29] Smits P,l~febvre V.Sox5 and Sox6 are required for uotochord extraeellular matrix sheath formation,notochord cell survival and development of the nucleus pulposus of intervertebral discs[J[.Development,2003,130(6):1135-1148.
[30] Erwin W M ,Ashman K,0 Donnel P,et a1. Nucleus pulposus notoehord cells secrete connective tissue growth factor and up—regulate proteoglycan expression by intervertebral disc chondrocytes[J].Arthritis Rheum,2006,54(12):3859—3867.
[31] Ali R,Le Maitre CL,Richardson SM,et a1.Connective tissue growth factor expression in human intervertebral disc : implications for angiogenesis in intervertebral disc degeneration[J].Biotech Histochem,2008,83(5):239—245.
[32] Erwin WM.1nman RD.Notochord cells regulate intervertebral disc chondrocyte proteoglycan production and cell proliferation[J].Spine,2006,31(10):1094-1099.
[33] Cappello R,Bird JL,Pfeifer D,et a1.Notochordal cell produce and assemble extracellular matrix in a distinct manner,which may be responsible for the maintenance of healthy nucleus pulposus[J].Spine,2006,31(8):873—882;discussion 883.
[34] Inui Y,Nishida K,Doita M, et a1.Fas-ligand expression Oil nucleus pulposus begins in developing embryo[J].Spine,2004,29(21):2365—2369.
[35] Kim KW ,Kim YS,Ha KY , et a1.An autoerine or paracrine Fas—mediated counterattack: potential mechanism for apoptosis of notoehordal cells in intact rat nucleus pulposus[J].Spine,2005,30(11):1247—1251.
[36] Kim KW ,Ha KY,Lee JS,et a1.The apoptotie effects of oxidative stress and antiapoptotic effects of easpase inhibitors on rat notoehordal cells[J].Spine,2007,32(22):2443—2448.
[37]张学森,丁惠强.退变颈椎间盘组织中细胞凋亡及相关蛋白Caspase一8、Caspase-9的表达fJJ.宁夏医学杂志,2008,30(4):295—297.
[38] 0 halloran DM ,Pandit AS.Tissue—engineering approach to regenerating theintevertebral disc [J].Tissue Eng,2007,13(8):1927—1954.
[39] Nesti IJ,Li WJ.Shanti RM.et a1.Intervertebral disc tissue engineering using a novel hyaluronic acid-nanofibrous seatfold (HANFS) amalgam[J].Tissue Eng Part A,2008,14(9):1527-1537
[40]Nishida K, Kang JD,Gilbertson LG,et a1. Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy:an study of adenovims·mediated transfer of the human transforming growth factor beta 1 encoding gene.Spine,1999,24:2419-2425.
[41]Nishida K, Kang JD,Suh JK,et a1.Adenovims-mediated gene transfer to nucleus pulposus ceHs : implications for the treatment of intervertebral disc degeneration.Spine。1998.23:2437-2443.
[42]Maldonado BA,Oegema TR Jr.Initial characterization of the metabolism of intervertebral disc ceHs encapsulated in miemspheres.J Orthop Res,1992,10:677-690.
[43]Wang IY, Baer AE,KIlns VB。et a1. Intervertebral disc ceUs exhibit diferences in gene expression in alginate and monolayer culture.Spine,20o1.26:1747.1751.
[44]Gan JC,Dueheyne P,Vresilovie EJ。et a1.Intervertebral disc tissue engineering II:cultures of nucleus pulposus cells.Clin Orthop Relat Res,20o3,(411):315-324.
[45]Gan JC,Dueheyne P,Vresilovie EJ。eta1.Intervertebral disc tissue engineering I:characterization of the nucleus pulposus.Clin Orthop Relat Res,2003。(4l1):305-314.
[46]Poiraudean S, Monteiro I, Anraet P. et a1. Phenoty0ic characteristics of rabbit intervertebral disc cells . Comparison with cartilage cells from the$~lTle animals.Spine. 1999.24:837-844.
[47]Gruber HE,Fisher EC Jr,Desai B。et a1.Human intervertebral disc cels from the ann Ius:three-dimensional culture in agaros or alginate and responsiveness to TGF-beta1.Exp Ceu Res.1997.235:13-21.
[48]Ra.vlnou F,Poiraudean S,FohzV。eta1.Monolayerannhsfibrosus cell cultures ina mechanically active environment:local culture condition adaptations and cel phenotype study. J Lab Clin Med,2Ooo.136 :412.421.
[49]AUIIi M ,LiW ,Markovic P,eta1.The potential andlimitations ofa cel1.seeded eolagen hyaluronan scafold to engineer an intervertebral disc-like matrix.Spine,20o3,28:446-454.
[50] Omlor GW, Lorenz H, Engelleiter K, et al. Changes in gene expression and protein distribution at different stages of mechanically induced disc degenerationan in vivo study on the New Zealand white rabbit. J Orthop Res2006;24:385–92.
[51] Mankin HJ, Lippiello L. The turnover of adult rabbit articular cartilage.J Bone Joint Surg Am 1969;51:1591–600.
[52] Watanabe H, Yamada Y, Kimata K. Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function. J Biochem (Tokyo)1998; 124:687–93.
[53] Verzijl N, DeGroot J, Thorpe SR, et al. Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem 2000;275:39027–31.
[54] Roughley PJ. Biology of intervertebral disc aging and degeneration: involvement of the extracellular matrix. Spine 2004;29:2691–9.
[55] Paul R, Haydon RC, Cheng H, et al. Potential use of Sox9 gene therapy for intervertebral degenerative disc disease. Spine 2003;28:755–63.
[56] Gruber HE, Norton HJ, Ingram JA, et al. The SOX9 transcription factor in the human disc: decreased immunolocalization with age and disc degeneration.Spine 2005;30:625–30.
[57] Kim DJ, Moon SH, Kim H, et al. Bone morphogenetic protein-2 facilitates expression of chondrogenic, not osteogenic, phenotype of human intervertebral disc cells.Spine 2003;28:2679–84.
[58] Thompson JP, Oegema TR Jr, Bradford DS. Stimulation of mature canine intervertebral disc by growth factors. Spine 1991;16:253–60.
[59] Shimer AL, Sobajima S, C. CR, et al. BMP-2 gene transfer favorably alters course ofdisc degeneration in rabbit model. Orthopaedic Research Society:Washington DC,ME,2005;0183.
[60] Peng B, Hao J, Hou S, et al. Possible pathogenesis of painful intervertebral disc degeneration. Spine 2006;31:560–6.