机械应力刺激对颈椎后纵韧带骨化的作用及其机制
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摘要
目的后纵韧带骨化症(OPLL)是后纵韧带异位骨化形成,压迫脊髓或神经根后出现脊髓损害或神经根刺激的症状,多发于颈椎,胸椎较少,鲜见于腰椎。其发病机制尚未完全清楚。临床研究发现,颈椎后路减压术后,OPLL患者后纵韧带骨化的发展进程加快,可能与术后颈椎稳定性被破坏有关。同时,国内外研究证实,在应力刺激下后纵韧带成纤维细胞具有成骨能力,碱性磷酸酶(ALP)、I型胶原(COL I)和骨钙素(OC)等表达升高,其机制仍在研究中。因此,探讨应力刺激对OPLL韧带细胞的影响和分子机制,对于我们了解该疾病的发生、发展机制有重要意义。ERK 1/2是MAPK家族的重要成员,阻断其上游MEK后将影响OPLL韧带细胞的成骨分化,同时ERK 1/2磷酸化水平也将发生变化。因此,ERK 1/2磷酸化水平可能在颈椎后纵韧带骨化形成及进展过程中发挥着重要的作用。磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKT)信号通路可以促进细胞增殖、分化以及抑制细胞凋亡,其可能在糖尿病患者OPLL发生过程中起重要作用,而且,机械应力刺激可以激活此通路,那么,AKT蛋白可能也在OPLL形成过程中发挥着重要作用。
方法选取2009年8月至2010年8月期间骨科住院病人,16例颈椎后纵韧带骨化和16例颈椎外伤的患者分别行颈前路手术治疗,术中切取韧带标本,无菌条件下置入装有生理盐水的无菌试管内,冰块保护下迅速送往细胞培养室。所有标本均采用自行改良的“组织块贴壁法”培养,将第3代细胞行细胞HE染色和波形蛋白鉴定。分别将两组(OPLL组与NOPLL组)第5代细胞接种于BioFlex 6孔板上,1%胎牛血清(FBS)同步化24h.采用美国FlexerCell公司生产的Flexercell4000细胞加载培养系统进行应力加载,设置参数为牵拉频率0.5 Hz,幅度10%,应力加载时间分别为6h和12h,以静止细胞作为对照,提取细胞总RNA和蛋白,应用real-time PCR和Western-blot技术分别检测两组细胞ALP、COL I、OC及核心转录因子(Runx2)表达量和ERK 1/2及AKT磷酸化水平的差异。然后,分别应用ERK 1/2及AKT蛋白上游阻断剂U0126和LY294002,以证实其作用机制。
结果应用自行改良的组织块转瓶贴壁法培养,细胞生长迅速,状态良好。培养7-9天后发现细胞从组织块周围爬出,镜下观察见韧带细胞呈多角形或梭形,细胞沿组织块周围排列。细胞HE染色胞浆粉红色染色较好,细胞核染色较淡;波形蛋白鉴定细胞呈多角形、梭形和圆形,细胞核呈圆形,较大,蓝染,胞浆为绿色,经鉴定为成纤维细胞。培养的细胞纯度较高,没有非成纤维细胞的污染。对两组细胞施加应力刺激后,对ALP、COL I、OC和Runx2的基因表达量进行检测发现,牵拉刺激后OPLL组升高较明显,12h组较静止组明显上调,差异具有统计学意义。而NOPLL组无明显变化。应用阻断剂后,OPLL组三个成骨指标RNA水平较未加阻断剂组下降,差异有统计学意义。
结论改良组织块培养法较传统的培养方法有一定优势。后纵韧带细胞呈多角形、梭形,胞浆内波形蛋白阳性表达。机械应力刺激可促进OPLL细胞成骨特异指标的表达,同时激活MEK/ERK1/2和PI3K/AKT信号通路。阻断上述通路后可抑制细胞ALP、COL I、OC的表达。这些结果说明应力刺激通过MEK/ERK1/2和PI3K/AKT调节OPLL细胞的成骨分化,ERK1/2和AKT蛋白的上调在后纵韧带骨化进展过程中的有重要作用。
Objective Ossification of the posterior longitudinal ligament (OPLL) is a pathological condition of spinal cord or nerve root compression caused by ectopic bone formation in the spinal ligament, which frequently occurs in cervical spine, and is seldom founded in thoracic spine and lumbar spine. The mechanism of OPLL development remains unclear. Some clinical studies reveal OPLL should develop after posterior cervical surgery in contrast with anterior cervical surgery. In addition, posterior longitudinal ligament fibroblasts should be osteogenic differentiation induced by the mechanical stress, such as gene expression promotion of alkaline phosphatase (ALP), collagen types I (COL I) and osteocalcin (OC). Therefore, it is very important to elucidate the development mechanism of the disease by exploring the role and mechanism of mechanical stress on spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. ERK 1/2 is one of MAPK family, which phosphorylation and osteogenic differentiation of OPLL cells should change after its upstream protein MEK blocked. Therefore, we postulated ERK1/2 phosphorylation should play an important role in advancing the progression of OPLL. It is the phosphatidylinositol-3-kinase/ protein kinase B (PI3K/AKT) signaling pathway, which could promote cell proliferation, inhibition of apoptosis and cell differentiation. The signaling pathway could be activated by mechanical stress and it also plays an important role in the onset and progression of OPLL suffered with diabetes mellitus. Then, it is likely to be significant of AKT protein for OPLL formation.
Methods Sixteen inpatients presenting with OPLL and sixteen NOPLL underwent anterior decompression between August 2009 and August 2010. Specimens of the posterior longitudinal ligaments which were extirpated carefully intraoperatively were put into an aseptic tubule filled with cold physiological saline and immediately transferred to the lab. All specimens were cultured with the modified“tissue fragment attachment-block”method. Hematoxylin eosin (HE) staining and immunostaining of vimentin were performed on the third passage cells. Fifth passage fibroblasts from OPLL and NOPLL patients were seeded on a BioFlex 6-well plate and incubated in DMEM supplemented with 1% FBS for 24 h. The Flexercell 4000 Tension Plus system (Flexercell International Corporation) was used to stretch the cells with mechanical stress of 10%, 0.5 Hz and respectively lasted 0h, 6h and 12 h. The expressions of RNA (ALP、COLI、OC and Runx2) and protein (ERK 1/2 and AKT) were detected. Then signaling pathway blocker, U0126 and LY294002, were used to clarify the mechanism.
Results All specimens were cultured with the modified“tissue fragment attachment-block”method and the isolated cells could proliferate rapidly and well in vitro. Cells were observed around the tissue fragment after 7-10 days culture and exhibited a fibroblast-like, spindle-shaped or polygon-shaped appearance. Cytoplasm was stained into deep pink and nucleus was stained into light blue in HE staining. Vimentin immunostaining of cells exhibited spindle-shaped or polygon-shaped appearance with large, round and blue nucleus and green cytoplasm. Cells were identified as fibroblasts and non-fibroblasts not found. The expressions of ALP, COL I, OC and Runx2 of OPLL cells were positively regulated after stimulation for 12h compared to the resting cells. Meanwhile, the osteogenic genes expression significantly up-regulated compared to the resting cells. However, there were no significant changes observed in NOPLL cells. The osteogenic genes expressions were significantly down-regulated with the signaling pathway blocker compared with the group without signaling pathway blocker.
Conclusions The modified“tissue fragment attachment-block”method had some advantages than the traditional one. Posterior longitudinal ligament cells exhibited spindle-shaped or polygon-shaped appearance and Vimentin immunostaining were positive. Mechanical stress could significantly promote the osteogenic genes expression and activate the MEK/ERK1/2 and PI3K/AKT pathway. Meanwhile, the osteogenic genes expressions of ALP、COL I、OC were significantly down-regulated with the signaling pathway blocker. Therefore, mechanical stress could induce osteogenic differentiation of spinal ligament cells derived from OPLL patients via these two signaling pathway, and ERK1/2 and AKT protein play important roles.
方法选取2009年8月至2010年8月期间骨科住院病人,16例颈椎后纵韧带骨化和16例颈椎外伤的患者分别行颈前路手术治疗,术中切取韧带标本,无菌条件下置入装有生理盐水的无菌试管内,冰块保护下迅速送往细胞培养室。所有标本均采用自行改良的“组织块贴壁法”培养,将第3代细胞行细胞HE染色和波形蛋白鉴定。分别将两组(OPLL组与NOPLL组)第5代细胞接种于BioFlex 6孔板上,1%胎牛血清(FBS)同步化24h.采用美国FlexerCell公司生产的Flexercell4000细胞加载培养系统进行应力加载,设置参数为牵拉频率0.5 Hz,幅度10%,应力加载时间分别为6h和12h,以静止细胞作为对照,提取细胞总RNA和蛋白,应用real-time PCR和Western-blot技术分别检测两组细胞ALP、COL I、OC及核心转录因子(Runx2)表达量和ERK 1/2及AKT磷酸化水平的差异。然后,分别应用ERK 1/2及AKT蛋白上游阻断剂U0126和LY294002,以证实其作用机制。
结果应用自行改良的组织块转瓶贴壁法培养,细胞生长迅速,状态良好。培养7-9天后发现细胞从组织块周围爬出,镜下观察见韧带细胞呈多角形或梭形,细胞沿组织块周围排列。细胞HE染色胞浆粉红色染色较好,细胞核染色较淡;波形蛋白鉴定细胞呈多角形、梭形和圆形,细胞核呈圆形,较大,蓝染,胞浆为绿色,经鉴定为成纤维细胞。培养的细胞纯度较高,没有非成纤维细胞的污染。对两组细胞施加应力刺激后,对ALP、COL I、OC和Runx2的基因表达量进行检测发现,牵拉刺激后OPLL组升高较明显,12h组较静止组明显上调,差异具有统计学意义。而NOPLL组无明显变化。应用阻断剂后,OPLL组三个成骨指标RNA水平较未加阻断剂组下降,差异有统计学意义。
结论改良组织块培养法较传统的培养方法有一定优势。后纵韧带细胞呈多角形、梭形,胞浆内波形蛋白阳性表达。机械应力刺激可促进OPLL细胞成骨特异指标的表达,同时激活MEK/ERK1/2和PI3K/AKT信号通路。阻断上述通路后可抑制细胞ALP、COL I、OC的表达。这些结果说明应力刺激通过MEK/ERK1/2和PI3K/AKT调节OPLL细胞的成骨分化,ERK1/2和AKT蛋白的上调在后纵韧带骨化进展过程中的有重要作用。
Objective Ossification of the posterior longitudinal ligament (OPLL) is a pathological condition of spinal cord or nerve root compression caused by ectopic bone formation in the spinal ligament, which frequently occurs in cervical spine, and is seldom founded in thoracic spine and lumbar spine. The mechanism of OPLL development remains unclear. Some clinical studies reveal OPLL should develop after posterior cervical surgery in contrast with anterior cervical surgery. In addition, posterior longitudinal ligament fibroblasts should be osteogenic differentiation induced by the mechanical stress, such as gene expression promotion of alkaline phosphatase (ALP), collagen types I (COL I) and osteocalcin (OC). Therefore, it is very important to elucidate the development mechanism of the disease by exploring the role and mechanism of mechanical stress on spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. ERK 1/2 is one of MAPK family, which phosphorylation and osteogenic differentiation of OPLL cells should change after its upstream protein MEK blocked. Therefore, we postulated ERK1/2 phosphorylation should play an important role in advancing the progression of OPLL. It is the phosphatidylinositol-3-kinase/ protein kinase B (PI3K/AKT) signaling pathway, which could promote cell proliferation, inhibition of apoptosis and cell differentiation. The signaling pathway could be activated by mechanical stress and it also plays an important role in the onset and progression of OPLL suffered with diabetes mellitus. Then, it is likely to be significant of AKT protein for OPLL formation.
Methods Sixteen inpatients presenting with OPLL and sixteen NOPLL underwent anterior decompression between August 2009 and August 2010. Specimens of the posterior longitudinal ligaments which were extirpated carefully intraoperatively were put into an aseptic tubule filled with cold physiological saline and immediately transferred to the lab. All specimens were cultured with the modified“tissue fragment attachment-block”method. Hematoxylin eosin (HE) staining and immunostaining of vimentin were performed on the third passage cells. Fifth passage fibroblasts from OPLL and NOPLL patients were seeded on a BioFlex 6-well plate and incubated in DMEM supplemented with 1% FBS for 24 h. The Flexercell 4000 Tension Plus system (Flexercell International Corporation) was used to stretch the cells with mechanical stress of 10%, 0.5 Hz and respectively lasted 0h, 6h and 12 h. The expressions of RNA (ALP、COLI、OC and Runx2) and protein (ERK 1/2 and AKT) were detected. Then signaling pathway blocker, U0126 and LY294002, were used to clarify the mechanism.
Results All specimens were cultured with the modified“tissue fragment attachment-block”method and the isolated cells could proliferate rapidly and well in vitro. Cells were observed around the tissue fragment after 7-10 days culture and exhibited a fibroblast-like, spindle-shaped or polygon-shaped appearance. Cytoplasm was stained into deep pink and nucleus was stained into light blue in HE staining. Vimentin immunostaining of cells exhibited spindle-shaped or polygon-shaped appearance with large, round and blue nucleus and green cytoplasm. Cells were identified as fibroblasts and non-fibroblasts not found. The expressions of ALP, COL I, OC and Runx2 of OPLL cells were positively regulated after stimulation for 12h compared to the resting cells. Meanwhile, the osteogenic genes expression significantly up-regulated compared to the resting cells. However, there were no significant changes observed in NOPLL cells. The osteogenic genes expressions were significantly down-regulated with the signaling pathway blocker compared with the group without signaling pathway blocker.
Conclusions The modified“tissue fragment attachment-block”method had some advantages than the traditional one. Posterior longitudinal ligament cells exhibited spindle-shaped or polygon-shaped appearance and Vimentin immunostaining were positive. Mechanical stress could significantly promote the osteogenic genes expression and activate the MEK/ERK1/2 and PI3K/AKT pathway. Meanwhile, the osteogenic genes expressions of ALP、COL I、OC were significantly down-regulated with the signaling pathway blocker. Therefore, mechanical stress could induce osteogenic differentiation of spinal ligament cells derived from OPLL patients via these two signaling pathway, and ERK1/2 and AKT protein play important roles.
引文
1.贾连顺,颈椎后纵韧带骨化并不都需要手术.中国矫形外科杂志, 2009. 17(7): p. 481-481.
2. Kim, T.J., K.W. Bae, W.S. Uhm, et al., Prevalence of ossification of the posterior longitudinal ligament of the cervical spine. Joint Bone Spine, 2008. 75(4): p. 471-4.
3.刘世文,张.,贾萍,张艳玲,关于颈椎后纵韧带骨化症的流行病学调查分析.白求恩医科大学学报, 1995. 21(4): p. 411-413.
4. Nakamura, H., [A radiographic study of the progression of ossification of the cervical posterior longitudinal ligament: the correlation between the ossification of the posterior longitudinal ligament and that of the anterior longitudinal ligament]. Nippon Seikeigeka Gakkai Zasshi, 1994. 68(9): p. 725-36.
5. Maigne, J.Y., X. AyralH. Guerin-Surville, Frequency and size of ossifications in the caudal attachments of the ligamentum flavum of the thoracic spine. Role of rotatory strains in their development. An anatomic study of 121 spines. Surg Radiol Anat, 1992. 14(2): p. 119-24.
6. Chen, J., X. Wang, C. Wang, et al., Rotational stress: Role in development of ossification of posterior longitudinal ligament and ligamentum flavum. Med Hypotheses, 2010.
7. Tanno, M., K.I. Furukawa, K. Ueyama, et al., Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003. 33(4): p. 475-84.
8. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004. 74(5): p. 448-57.
9. Iwasawa, T., K. Iwasaki, T. Sawada, et al., Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Tissue Int, 2006. 79(6): p. 422-30.
10. Sawada, T., M. Kishiya, K. Kanemaru, et al., Possible role of extracellular nucleotides in ectopic ossification of human spinal ligaments. J Pharmacol Sci, 2008. 106(1): p. 152-61.
11.戴力扬,激素和生长因子在脊柱韧带骨化发生机制中的作用.上海第二医科大学学报, 2004. 24(2): p. 143-146.
12.孔清泉,脊柱韧带骨化相关的易感基因研究进展.中华外科杂志, 2007. 45(20): p. 1435-1437.
13. Terayama, K., Genetic studies on ossification of the posterior longitudinal ligament of the spine. Spine(Phila Pa 1976), 1989. 14(11): p. 1184-91.
14. Ikegawa, S., [Updates on ossification of posterior longitudinal ligament. Genetic approach to the susceptibility genes for ossification of posterior longitudinal ligament of the spine (OPLL) and for its molecular pathogenesis]. Clin Calcium, 2009. 19(10): p. 1457-61.
15. Koga, H., T. Sakou, E. Taketomi, et al., Genetic mapping of ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet, 1998. 62(6): p. 1460-7.
16. Matsunaga, S., [Updates on ossification of posterior longitudinal ligament. Epidemiology and pathogenesis of OPLL]. Clin Calcium, 2009. 19(10): p. 1415-20.
17. Sakou, T., E. Taketomi, S. Matsunaga, et al., Genetic study of ossification of the posterior longitudinal ligament in the cervical spine with human leukocyte antigen haplotype. Spine (Phila Pa 1976), 1991. 16(11): p. 1249-52.
18.刘洋,脊柱后纵韧带骨化性疾病的基础研究进展.脊柱外科杂志, 2010. 8(2): p. 120-123.
19. Tsukahara, S., N. Miyazawa, H. Akagawa, et al., COL6A1, the candidate gene for ossification of the posterior longitudinal ligament, is associated with diffuse idiopathic skeletal hyperostosis in Japanese. Spine (Phila Pa 1976), 2005. 30(20): p. 2321-4.
20. Kim, T.J., T.H. Kim, J.B. Jun, et al., Prevalence of ossification of posterior longitudinal ligament in patients with ankylosing spondylitis. J Rheumatol, 2007. 34(12): p. 2460-2.
21. Hori T, K.Y., Kimura T., How does the ossification area of the posterior longitudinal ligament progress after cervical laminoplasty? Spine (Phila Pa 1976). , 2006. 31(24): p. 2807-12.
22. Matsunaga, S., H. Koga, N. Kawabata, et al., Ossification of the posterior longitudinal ligament in dizygotic twins with schizophrenia: a case report. Mod Rheumatol, 2008. 18(3): p. 277-80.
23.王冰,吴燕红,杨志等, MAPK/ERK信号转导通路的分子生物学特征及生物效应.第四军医大学学报, 2005. 26(suppl): p. 18-21.
24. Courchesne WE, K.R., Thorner J., A putative protein kinase overcomes comes pheromome-induced arrest of cell cycling in S.cerevisiae. cell, 1989. 58: p. 1107一1119.
25. Boulton, T.G., S.H. Nye, D.J. Robbins, et al., ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. cell, 1991. 65(4): p. 663-75.
26. Cobb, M.H., D.J. RobbinsT.G. Boulton, ERKs, extracellular signal-regulated MAP-2 kinases. Curr Opin Cell Biol, 1991. 3(6): p. 1025-32.
27. Widmann, C., S. Gibson, M.B. Jarpe, et al., Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev, 1999. 79(1): p. 143-80.
28. Chang, L.M. Karin, Mammalian MAP kinase signalling cascades. Nature, 2001. 410(6824): p. 37-40.
29. Katso, R.M., O.E. Pardo, A. Palamidessi, et al., Phosphoinositide 3-Kinase C2beta regulatescytoskeletal organization and cell migration via Rac-dependent mechanisms. Mol Biol Cell, 2006. 17(9): p. 3729-44.
30. Katso, R., K. Okkenhaug, K. Ahmadi, et al., Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol, 2001. 17: p. 615-75.
31. Coffey, J.C., J.H. Wang, M.J. Smith, et al., Phosphoinositide 3-kinase accelerates postoperative tumor growth by inhibiting apoptosis and enhancing resistance to chemotherapy-induced apoptosis. Novel role for an old enemy. J Biol Chem, 2005. 280(22): p. 20968-77.
32.孙晓杰,黄常志, PI3K-Akt信号通路与肿瘤.世界华人消化杂志, 2006. 14(3): p. 306-311.
33. Yuan, Z.Q., R.I. Feldman, G.E. Sussman, et al., AKT2 inhibition of cisplatin-induced JNK/p38 and Bax activation by phosphorylation of ASK1: implication of AKT2 in chemoresistance. J Biol Chem, 2003. 278(26): p. 23432-40.
34. Yokoi, K.I.J. Fidler, Hypoxia increases resistance of human pancreatic cancer cells to apoptosis induced by gemcitabine. Clin Cancer Res, 2004. 10(7): p. 2299-306.
35.朱俊峰,不同强度张应力对成骨细胞分化和MAPK磷酸化的影响.上海交通大学博士学位论文, 2009.
36. Furukawa, K., Current topics in pharmacological research on bone metabolism: molecular basis of ectopic bone formation induced by mechanical stress. J Pharmacol Sci, 2006. 100(3): p. 201-4.
1.董军,袁.文,王新伟,等.颈椎后纵韧带骨化成纤维细胞的培养及其生物学特性.脊柱外科杂志, 2007. 5(2): p. 109-112.
2. Tanno, M., K.I. Furukawa, K. Ueyama, et al., Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003. 33(4): p. 475-84.
3. Li, H., D. Liu, C.Q. Zhao, et al., High glucose promotes collagen synthesis by cultured cells from rat cervical posterior longitudinal ligament via transforming growth factor-beta1. Eur Spine J, 2008. 17(6): p. 873-81.
4. Li, H., D. Liu, C.Q. Zhao, et al., Insulin potentiates the proliferation and bone morphogenetic protein-2-induced osteogenic differentiation of rat spinal ligament cells via extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. Spine (Phila Pa 1976), 2008. 33(22): p. 2394-402.
5. Iwasawa, T., K. Iwasaki, T. Sawada, et al., Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Tissue Int, 2006. 79(6): p. 422-30.
6. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004. 74(5): p. 448-57.
1. Tsukamoto, N., T. Maeda, H. Miura, et al., Repetitive tensile stress to rat caudal vertebrae inducing cartilage formation in the spinal ligaments: a possible role of mechanical stress in the development of ossification of the spinal ligaments. J Neurosurg Spine, 2006. 5(3): p. 234-42.
2. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004. 74(5): p. 448-57.
3. Tanno, M., K.I. Furukawa, K. Ueyama, et al., Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003. 33(4): p. 475-84.
4. Qi, J., L. Chi, J. Wang, et al., Modulation of collagen gel compaction by extracellular ATP is MAPK and NF-kappaB pathways dependent. Exp Cell Res, 2009. 315(11): p. 1990-2000.
5. Granet, C., A.G. Vico, C. Alexandre, et al., MAP and src kinases control the induction of AP-1 members in response to changes in mechanical environment in osteoblastic cells. Cell Signal, 2002. 14(8): p. 679-88.
6. Granet, C., N. Boutahar, L. Vico, et al., MAPK and SRC-kinases control EGR-1 and NF-kappa B inductions by changes in mechanical environment in osteoblasts. Biochem Biophys Res Commun, 2001. 284(3): p. 622-31.
7. Jilka, R.L., R.S. Weinstein, T. Bellido, et al., Osteoblast programmed cell death (apoptosis): modulation by growth factors and cytokines. J Bone Miner Res, 1998. 13(5): p. 793-802.
8.刘洋,李刚,李建福,付小兵.细胞机械应力响应的生物学基础及机制研究进展中国美容医学, 2007. 16(3): p. 421-423.
9. Cantiello, H.F., Role of the actin cytoskeleton on epithelial Na+ channel regulation. Kidney Int, 1995. 48(4): p. 970-84.
10. Doyle, A.M., R.M. NeremT. Ahsan, Human mesenchymal stem cells form multicellular structures in response to applied cyclic strain. Ann Biomed Eng, 2009. 37(4): p. 783-93.
11. Molitoris, B.A., Putting the actin cytoskeleton into perspective: pathophysiology of ischemic alterations. Am J Physiol, 1997. 272(4 Pt 2): p. F430-3.
12. Dartsch, P.C.E. Betz, Response of cultured endothelial cells to mechanical stimulation. Basic Res Cardiol, 1989. 84(3): p. 268-81.
13. Wang, J.H., P. Goldschmidt-Clermont, J. Wille, et al., Specificity of endothelial cell reorientation in response to cyclic mechanical stretching. J Biomech, 2001. 34(12): p. 1563-72.
14. Hayakawa, K., N. SatoT. Obinata, Dynamic reorientation of cultured cells and stress fibers under mechanical stress from periodic stretching. Exp Cell Res, 2001. 268(1): p. 104-14.
15. Sanchez-Esteban, J., Y. Wang, L.A. Cicchiello, et al., Cyclic mechanical stretch inhibits cell proliferation and induces apoptosis in fetal rat lung fibroblasts. Am J Physiol Lung Cell Mol Physiol, 2002. 282(3): p. L448-56.
16. Kobayashi, Y., F. Hashimoto, H. Miyamoto, et al., Force-induced osteoclast apoptosis in vivo is accompanied by elevation in transforming growth factor beta and osteoprotegerin expression. J Bone Miner Res, 2000. 15(10): p. 1924-34.
1. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004. 74(5): p. 448-57.
2. Tanno, M., K.I. Furukawa, K. Ueyama, et al., Uniaxial cyclic stretch induces osteogenicdifferentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003. 33(4): p. 475-84.
3. Trieb, K., H. BlahovecB. Kubista, Effects of hyperthermia on heat shock protein expression, alkaline phosphatase activity and proliferation in human osteosarcoma cells. Cell Biochem Funct, 2007. 25(6): p. 669-72.
4. Oyajobi, B.O., I.R. Garrett, A. Gupta, et al., Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease. Br J Haematol, 2007. 139(3): p. 434-8.
5. Fukumoto, S., [PTH and mechanical stress]. Clin Calcium, 2008. 18(9): p. 1327-31.
6. Jiang, J.X., A.J. Siller-JacksonS. Burra, Roles of gap junctions and hemichannels in bone cell functions and in signal transmission of mechanical stress. Front Biosci, 2007. 12: p. 1450-62.
7. Sawada, T., M. Kishiya, K. Kanemaru, et al., Possible role of extracellular nucleotides in ectopic ossification of human spinal ligaments. J Pharmacol Sci, 2008. 106(1): p. 152-61.
8. Iwasawa, T., K. Iwasaki, T. Sawada, et al., Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Tissue Int, 2006. 79(6): p. 422-30.
9. Ito, Y.Y.W. Zhang, A RUNX2/PEBP2alphaA/CBFA1 mutation in cleidocranial dysplasia revealing the link between the gene and Smad. J Bone Miner Metab, 2001. 19(3): p. 188-94.
10. Thirunavukkarasu, K., M. Mahajan, K.W. McLarren, et al., Two domains unique to osteoblast-specific transcription factor Osf2/Cbfa1 contribute to its transactivation function and its inability to heterodimerize with Cbfbeta. Mol Cell Biol, 1998. 18(7): p. 4197-208.
11. Xiao, Z.S., L.G. SimpsonL.D. Quarles, IRES-dependent translational control of Cbfa1/Runx2 expression. J Cell Biochem, 2003. 88(3): p. 493-505.
12. Ducy, P., R. Zhang, V. Geoffroy, et al., Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell, 1997. 89(5): p. 747-54.
1. Ziros, P.G., A.P. Gil, T. Georgakopoulos, et al., The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells. J Biol Chem, 2002. 277(26): p. 23934-41.
2. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament.Calcif Tissue Int, 2004. 74(5): p. 448-57.
3. Xiao, G., D. Jiang, P. Thomas, et al., MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J Biol Chem, 2000. 275(6): p. 4453-9.
4. Kanno, T., T. Takahashi, T. Tsujisawa, et al., Mechanical stress-mediated Runx2 activation is dependent on Ras/ERK1/2 MAPK signaling in osteoblasts. J Cell Biochem, 2007. 101(5): p. 1266-77.
5. Granet, C., A.G. Vico, C. Alexandre, et al., MAP and src kinases control the induction of AP-1 members in response to changes in mechanical environment in osteoblastic cells. Cell Signal, 2002. 14(8): p. 679-88.
6. Liu, L., W. YuanJ. Wang, Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress. Biomech Model Mechanobiol, 2010.
7. Danciu, T.E., R.M. Adam, K. Naruse, et al., Calcium regulates the PI3K-Akt pathway in stretched osteoblasts. FEBS Lett, 2003. 536(1-3): p. 193-7.
8. Lee, D.Y., Y.S. Li, S.F. Chang, et al., Oscillatory flow-induced proliferation of osteoblast-like cells is mediated by alphavbeta3 and beta1 integrins through synergistic interactions of focal adhesion kinase and Shc with phosphatidylinositol 3-kinase and the Akt/mTOR/p70S6K pathway. J Biol Chem, 2010. 285(1): p. 30-42.
9. Lin, T.H., C.H. Tang, S.Y. Hung, et al., Upregulation of heme oxygenase-1 inhibits the maturation and mineralization of osteoblasts. J Cell Physiol, 2010. 222(3): p. 757-68.
10. Olkku, A., J.J. Leskinen, M.J. Lammi, et al., Ultrasound-induced activation of Wnt signaling in human MG-63 osteoblastic cells. Bone, 2010. 47(2): p. 320-30.
11. Triplett, J.W., R. O'Riley, K. Tekulve, et al., Mechanical loading by fluid shear stress enhances IGF-1 receptor signaling in osteoblasts in a PKCzeta-dependent manner. Mol Cell Biomech, 2007. 4(1): p. 13-25.
12. Takai, S., H. Tokuda, Y. Hanai, et al., Activation of phosphatidylinositol 3-kinase/Akt limits FGF-2-induced VEGF release in osteoblasts. Mol Cell Endocrinol, 2007. 267(1-2): p. 46-54.
13. Norvell, S.M., M. Alvarez, J.P. Bidwell, et al., Fluid shear stress induces beta-catenin signaling in osteoblasts. Calcif Tissue Int, 2004. 75(5): p. 396-404.
14. Chang, E.J., H.H. Kim, J.E. Huh, et al., Low proliferation and high apoptosis of osteoblastic cells on hydrophobic surface are associated with defective Ras signaling. Exp Cell Res, 2005. 303(1): p. 197-206.
15. Xia, X., N. Batra, Q. Shi, et al., Prostaglandin promotion of osteocyte gap junction function through transcriptional regulation of connexin 43 by glycogen synthase kinase 3/beta-catenin signaling. Mol Cell Biol, 2010. 30(1): p. 206-19.
16. Li, H., D. Liu, C.Q. Zhao, et al., Insulin potentiates the proliferation and bone morphogenetic protein-2-induced osteogenic differentiation of rat spinal ligament cells via extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. Spine (Phila Pa 1976), 2008. 33(22): p. 2394-402.
1. Nakamura, H., [A radiographic study of the progression of ossification of the cervical posterior longitudinal ligament: the correlation between the ossification of the posterior longitudinal ligament and that of the anterior longitudinal ligament]. Nippon Seikeigeka Gakkai Zasshi, 1994. 68(9): p. 725-36.
2. Tsukamoto, N., T. Maeda, H. Miura, et al., Repetitive tensile stress to rat caudal vertebrae inducing cartilage formation in the spinal ligaments: a possible role of mechanical stress in the development of ossification of the spinal ligaments. J Neurosurg Spine, 2006. 5(3): p. 234-42.
3. Tanno, M., K.I. Furukawa, K. Ueyama, et al., Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003. 33(4): p. 475-84.
4. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004. 74(5): p. 448-57.
5. Iwasawa, T., K. Iwasaki, T. Sawada, et al., Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Tissue Int, 2006. 79(6): p. 422-30.
6. Sawada, T., M. Kishiya, K. Kanemaru, et al., Possible role of extracellular nucleotides in ectopic ossification of human spinal ligaments. J Pharmacol Sci, 2008. 106(1): p. 152-61.
7.戴力扬,激素和生长因子在脊柱韧带骨化发生机制中的作用.上海第二医科大学学报, 2004. 24(2): p. 143-146.
8.孔清泉,脊柱韧带骨化相关的易感基因研究进展.中华外科杂志, 2007. 45(20): p. 1435-1437.
9. Terayama, K., Genetic studies on ossification of the posterior longitudinal ligament of the spine. Spine (Phila Pa 1976), 1989. 14(11): p. 1184-91.
10. Ikegawa, S., [Updates on ossification of posterior longitudinal ligament. Genetic approach to the susceptibility genes for ossification of posterior longitudinal ligament of the spine (OPLL) and for its molecular pathogenesis]. Clin Calcium, 2009. 19(10): p. 1457-61.
11. Koga, H., T. Sakou, E. Taketomi, et al., Genetic mapping of ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet, 1998. 62(6): p. 1460-7.
12. Matsunaga, S., [Updates on ossification of posterior longitudinal ligament. Epidemiology and pathogenesis of OPLL]. Clin Calcium, 2009. 19(10): p. 1415-20.
13. Tsukahara, S., N. Miyazawa, H. Akagawa, et al., COL6A1, the candidate gene for ossification of the posterior longitudinal ligament, is associated with diffuse idiopathic skeletal hyperostosis in Japanese. Spine (Phila Pa 1976), 2005. 30(20): p. 2321-4.
14. Kim, T.J., T.H. Kim, J.B. Jun, et al., Prevalence of ossification of posterior longitudinal ligament in patients with ankylosing spondylitis. J Rheumatol, 2007. 34(12): p. 2460-2.
15. Hori T, K.Y., Kimura T., How does the ossification area of the posterior longitudinal ligament progress after cervical laminoplasty? Spine (Phila Pa 1976). , 2006. 31(24): p. 2807-12.
16. Matsunaga, S., H. Koga, N. Kawabata, et al., Ossification of the posterior longitudinal ligament in dizygotic twins with schizophrenia: a case report. Mod Rheumatol, 2008. 18(3): p. 277-80.
17. Danciu, T.E., R.M. Adam, K. Naruse, et al., Calcium regulates the PI3K-Akt pathway in stretchedosteoblasts. FEBS Lett, 2003. 536(1-3): p. 193-7.
18. Lee, D.Y., Y.S. Li, S.F. Chang, et al., Oscillatory flow-induced proliferation of osteoblast-like cells is mediated by alphavbeta3 and beta1 integrins through synergistic interactions of focal adhesion kinase and Shc with phosphatidylinositol 3-kinase and the Akt/mTOR/p70S6K pathway. J Biol Chem, 2010. 285(1): p. 30-42.
19. Lin, T.H., C.H. Tang, S.Y. Hung, et al., Upregulation of heme oxygenase-1 inhibits the maturation and mineralization of osteoblasts. J Cell Physiol, 2010. 222(3): p. 757-68.
20. Olkku, A., J.J. Leskinen, M.J. Lammi, et al., Ultrasound-induced activation of Wnt signaling in human MG-63 osteoblastic cells. Bone, 2010. 47(2): p. 320-30.
21. Triplett, J.W., R. O'Riley, K. Tekulve, et al., Mechanical loading by fluid shear stress enhances IGF-1 receptor signaling in osteoblasts in a PKCzeta-dependent manner. Mol Cell Biomech, 2007. 4(1): p. 13-25.
22. Takai, S., H. Tokuda, Y. Hanai, et al., Activation of phosphatidylinositol 3-kinase/Akt limits FGF-2-induced VEGF release in osteoblasts. Mol Cell Endocrinol, 2007. 267(1-2): p. 46-54.
23. Norvell, S.M., M. Alvarez, J.P. Bidwell, et al., Fluid shear stress induces beta-catenin signaling in osteoblasts. Calcif Tissue Int, 2004. 75(5): p. 396-404.
24. Chang, E.J., H.H. Kim, J.E. Huh, et al., Low proliferation and high apoptosis of osteoblastic cells on hydrophobic surface are associated with defective Ras signaling. Exp Cell Res, 2005. 303(1): p. 197-206.
25. Xia, X., N. Batra, Q. Shi, et al., Prostaglandin promotion of osteocyte gap junction function through transcriptional regulation of connexin 43 by glycogen synthase kinase 3/beta-catenin signaling. Mol Cell Biol, 2010. 30(1): p. 206-19.
1贾连顺.颈椎后纵韧带骨化并不都需要手术.中国矫形外科杂志, 2009; 17(7):481
2 Kim TJ, Bae KW, Uhm WS, et al. Prevalence of ossification of the posterior longitudinal ligament of the cervical spine. Joint Bone Spine, 2008; 75(4):471-474
3 Hirabayashi K, Miyakawa J, Satomi K, et al. Operative results and postoperative progression of ossification among patients with ossification of cervical posterior longitudinal ligament. Spine(Phila Pa 1976), 1981; 6(4):354-364
4 Epstein NE. Ossification of the posterior longitudinal ligament in evolution in 12 patients. Spine(Phila Pa 1976), 1994; 19(6):673-701
5 Murakami M, Seichi A, Chikuda H, et al. Long-term follow-up of the progression of ossification of the posterior longitudinal ligament. J Neurosurg Spine, 2010; 12(5):577-579
6 Honda H. Histopathological study of aging of the posterior portion of human cervical vertebral bodies and discs with special reference to the early ossification of the posterior longitudinal ligament. Nippon Seikeigeka Gakkai Zasshi, 1983; 57(12):1881-1893
7 Ono K, Yonenobu K, Miyamoto S, et al. Pathology of ossification of the posterior longitudinal ligament and ligamentum flavum. Clin Orthop Relat Res, 1999; 359:18-26
8 Yoshizawa T, Naitoh Y, Yoshida M, et al. Cervical myelopathy due to hypertrophy of the posterior longitudinal ligament (HPLL): a case report. Rinsho Shinkeigaku, 1991; 31(7):720-724
9 Mizuno J, Nakagawa H, Hashizume Y. Myelopathy caused by hypertrophy of the posterior longitudinal ligament of the cervical spine in a patient with long-term hemodialysis. No Shinkei Geka, 1996; 24(7):655-659
10 Song J, Mizuno J, Hashizume Y, et al. Immunohistochemistry of symptomatic hypertrophy of the posterior longitudinal ligament with special reference to ligamentous ossification. Spinal Cord, 2006; 44(9):576-581
11戴力扬.激素和生长因子在脊柱韧带骨化发生机制中的作用.上海第二医科大学学报, 2004; 24(2):143-146
12 Kobashi G, Ohta K, Washio M, et al. FokI variant of vitamin D receptor gene and factors related to atherosclerosis associated with ossification of the posterior longitudinal ligament of the spine: a multi-hospital case-control study. Spine(Phila Pa 1976), 2008; 33(16):E553-E558
13 Ito K, Matsuyama Y, Yukawa Y, et al. Analysis of interleukin-8, interleukin-10, and tumor necrosis factor-alpha in the cerebrospinal fluid of patients with cervical spondylotic myelopathy. J Spinal Disord Tech, 2008; 21(2):145-147
14 Kishiya M, Sawada T, Kanemaru K, et al. A functional RNAi screen for Runx2-regulated genes associated with ectopic bone formation in human spinal ligaments. J Pharmacol Sci, 2008; 106(3):404-414
15 Li H, Liu D, Zhao CQ, et al. Insulin potentiates the proliferation and bone morphogenetic protein-2-induced osteogenic differentiation of rat spinal ligament cells via extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. Spine(Phila Pa 1976), 2008; 33(22):2394-2402
16 Li H, Liu D, Zhao CQ, et al. High glucose promotes collagen synthesis by cultured cells from rat cervical posterior longitudinal ligament via transforming growth factor-beta1. Eur Spine J, 2008; 17(6):873-881
17 Eun JP, Ma TZ, Lee WJ, et al. Comparative analysis of serum proteomes to discover biomarkers for ossification of the posterior longitudinal ligament. Spine(Phila Pa 1976), 2007; 32(7):728-734
18张颖.颈椎后纵韧带骨化症发病机制的比较蛋白组学研究[D].第二军医大学博士学位论文, 2008
19 Nakamura H. A radiographic study of the progression of ossification of the cervical posterior longitudinal ligament: the correlation between the ossification of the posterior longitudinal ligament and that of the anterior longitudinal ligament. Nippon Seikeigeka Gakkai Zasshi, 1994; 68(9):725-736
20 Tsukamoto N, Maeda T, Miura H, et al. Repetitive tensile stress to rat caudal vertebrae inducing cartilage formation in the spinal ligaments: a possible role of mechanical stress in the development of ossification of the spinal ligaments. J Neurosurg Spine, 2006; 5(3):234-242
21 Miyazawa N, Akiyama I. Ossification of the ligamentum flavum of the cervical spine. J Neurosurg Sci, 2007; 51(3):139-144
22谭炳毅,贾连顺,王海燕,等.应力刺激对于后纵韧带骨化因子的影响.中国矫形外科杂志, 2006; 14(13):1013-1015
23向选平,金涛,王华,等.手术刺激对腰椎后纵韧带内BMP-2及BMP-7 mRNA表达的影响.中国现代医学杂志, 2010; 20(6):858-864
24 Maigne JY, Ayral X, Guerin-Surville H. Frequency and size of ossifications in the caudal attachments of theligamentum flavum of the thoracic spine. Role of rotatory strains in their development. An anatomic study of 121 spines. Surg Radiol Anat, 1992; 14(2):119-124
25 Chen J, Wang X, Wang C, et al. Rotational stress: Role in development of ossification of posterior longitudinal ligament and ligamentum flavum. Med Hypotheses, 2010;[Epub ahead of print]
26 Tanno M, Furukawa KI, Ueyama K, et al. Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003; 33(4):475-484
27 Iwasaki K, Furukawa KI, Tanno M, et al. Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004; 74(5):448-457
28 Iwasawa T, Iwasaki K, Sawada T, et al. Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Tissue Int, 2006; 79(6):422-430
29 Sawada T, Kishiya M, Kanemaru K, et al. Possible role of extracellular nucleotides in ectopic ossification of human spinal ligaments. J Pharmacol Sci, 2008; 106(1):152-161
30 Azuma Y, Kato Y, Taguchi T. Etiology of cervical myelopathy induced by ossification of the posterior longitudinal ligament: determining the responsible level of OPLL myelopathy by correlating static compression and dynamic factors. J Spinal Disord Tech, 2010; 23(3):166-169
31 Fujiyoshi T, Yamazaki M, Okawa A, et al. Static versus dynamic factors for the development of myelopathy in patients with cervical ossification of the posterior longitudinal ligament. J Clin Neurosci, 2010; 17(3):320-324
32 Kato Y, Kanchiku T, Imajo Y, et al. Biomechanical study of the effect of degree of static compression of the spinal cord in ossification of the posterior longitudinal ligament. J Neurosurg Spine, 2010; 12(3):301-305
33 Nakae R, Onda H, Yokobori S, et al. Clinical analysis of spinal cord injury with or without cervical ossification of the posterior longitudinal ligament, spondylosis, and canal stenosis in elderly head injury patients. Neurol Med Chir(Tokyo), 2010; 50(6):461-465
34 Yoo DS, Lee SB, Huh PW, et al. Spinal cord injury in cervical spinal stenosis by minor trauma. World Neurosurg, 2010; 73(1):50-52
35 Sugimoto Y, Ito Y, Tanaka M, et al. Cervical cord injury in patients with ankylosed spines: progressive paraplegia in two patients after posterior fusion without decompression. Spine(Phila Pa 1976), 2009; 34(23):E861-E863
36 Tsukahara S, Miyazawa N, Akagawa H, et al. COL6A1, the candidate gene for ossification of the posterior longitudinal ligament, is associated with diffuse idiopathic skeletal hyperostosis in Japanese. Spine (Phila Pa 1976), 2005; 30(20):2321-2324
37 Kim TJ, Kim TH, Jun JB, et al. Prevalence of ossification of posterior longitudinal ligament in patients with ankylosing spondylitis. J Rheumatol, 2007; 34(12):2460-2462
38 Hori T, Kawaguchi Y, Kimura T. How does the ossification area of the posterior longitudinal ligament progress after cervical laminoplasty Spine(Phila Pa 1976), 2006; 31(24):2807-2812
39 Matsunaga S, Koga H, Kawabata N, et al. Ossification of the posterior longitudinal ligament in dizygotic twins with schizophrenia: a case report. Mod Rheumatol, 2008; 18(3):277-280
[1] Matsunaga S., Sakou T., Taketomi E., et al. The natural course of myelopathy caused by ossification of the posterior longitudinal ligament in the cervical spine. Clin Orthop Relat Res,1994; (305):168-77.
[2] Miyazawa N., Akiyama I. Ossification of the ligamentum flavum of the cervical spine. J Neurosurg Sci,2007; 51(3):139-44.
[3]秦德安,李晓东,崔新刚,刘峰.胸椎椎板倾斜角在胸椎黄韧带骨化中的解剖学意义.中国临床解剖学杂志,2006; 24(6):634-636.
[4] Chen Y., Lu X. H., Yang L. L., et al. Ossification of ligamentum flavum related to thoracic kyphosis after tuberculosis: case report and review of the literature. Spine (Phila Pa 1976),2009; 34(1):E41-4.
[5] Maigne J. Y., Ayral X., Guerin-Surville H. Frequency and size of ossifications in the caudal attachments of the ligamentum flavum of the thoracic spine. Role of rotatory strains in their development. An anatomic study of 121 spines. Surg Radiol Anat,1992; 14(2):119-24.
[6] Chen J., Wang X., Wang C., et al. Rotational stress: Role in development of ossification of posterior longitudinal ligament and ligamentum flavum. Med Hypotheses,2010.
[7] Hale J. J., Gruson K. I., Spivak J. M. Laminoplasty: a review of its role in compressive cervical myelopathy. Spine J,2006; 6(6 Suppl):289S-298S.
[8] Sugimoto Y., Ito Y., Tanaka M., et al. Cervical cord injury in patients with ankylosed spines: progressive paraplegia in two patients after posterior fusion without decompression. Spine (Phila Pa 1976),2009; 34(23):E861-3.
[9] Takatsu T., Ishida Y., Suzuki K., et al. Radiological study of cervical ossification of the posterior longitudinal ligament. J Spinal Disord,1999; 12(3):271-3.
[10] Hirabayashi K., Miyakawa J., Satomi K., et al. Operative results and postoperative progression ofossification among patients with ossification of cervical posterior longitudinal ligament. Spine (Phila Pa 1976),1981; 6(4):354-64.
[11] Nakamura H. [A radiographic study of the progression of ossification of the cervical posterior longitudinal ligament: the correlation between the ossification of the posterior longitudinal ligament and that of the anterior longitudinal ligament]. Nippon Seikeigeka Gakkai Zasshi,1994; 68(9):725-36.
[12] Kawaguchi Y., Kanamori M., Ishihara H., et al. Progression of ossification of the posterior longitudinal ligament following en bloc cervical laminoplasty. J Bone Joint Surg Am,2001; 83-A(12):1798-802.
[13] Tokuhashi Y., Ajiro Y., Umezawa N. A patient with two re-surgeries for delayed myelopathy due to progression of ossification of the posterior longitudinal ligaments after cervical laminoplasty. Spine (Phila Pa 1976),2009; 34(2):E101-5.
[14] Li F., Chen Q., Xu K. Surgical treatment of 40 patients with thoracic ossification of the ligamentum flavum. J Neurosurg Spine,2006; 4(3):191-7.
[15] Wang W., Kong L. Ossification of ligamentum. J Neurosurg Spine,2007; 6(1):96; author reply 96-7.
[16] Tateiwa Y., Kamimura M., Itoh H., et al. Multilevel subtotal corpectomy and interbody fusion using a fibular bone graft for cervical myelopathy due to ossification of the posterior longitudinal ligament. J Clin Neurosci,2003; 10(2):199-207.
[17] Furusawa N., Baba H., Imura S., et al. Characteristics and mechanism of the ossification of posterior longitudinal ligament in the tip-toe walking Yoshimura (twy) mouse. Eur J Histochem,1996; 40(3):199-210.
[18] Tsukamoto N., Maeda T., Miura H., et al. Repetitive tensile stress to rat caudal vertebrae inducing cartilage formation in the spinal ligaments: a possible role of mechanical stress in the development of ossification of the spinal ligaments. J Neurosurg Spine,2006; 5(3):234-42.
[19]谭炳毅;贾连顺;王海燕;蔡国栋;董军;.应力刺激对于后纵韧带骨化因子的影响.中国矫形外科杂志,2006; 13.
[20]向选平,金涛,王华等.手术刺激对腰椎后纵韧带内BMP-2及BMP-7 mRNA表达的影响.中国现代医学杂志,2010; 20(6):858-864.
[21] Tanno M., Furukawa K. I., Ueyama K., et al. Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone,2003; 33(4):475-84.
[22] Iwasaki K., Furukawa K. I., Tanno M., et al. Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int,2004; 74(5):448-57.
[23] Iwasawa T., Iwasaki K., Sawada T., et al. Pathophysiological role of endothelin in ectopic ossification ofhuman spinal ligaments induced by mechanical stress. Calcif Tissue Int,2006; 79(6):422-30.
[24] Ohishi H., Furukawa K., Iwasaki K., et al. Role of prostaglandin I2 in the gene expression induced by mechanical stress in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. J Pharmacol Exp Ther,2003; 305(3):818-24.
[25]杨海松. Connexin43在机械应力诱导颈椎后纵韧带骨化进展过程中的作用研究[D].第二军医大学,2010.
2. Kim, T.J., K.W. Bae, W.S. Uhm, et al., Prevalence of ossification of the posterior longitudinal ligament of the cervical spine. Joint Bone Spine, 2008. 75(4): p. 471-4.
3.刘世文,张.,贾萍,张艳玲,关于颈椎后纵韧带骨化症的流行病学调查分析.白求恩医科大学学报, 1995. 21(4): p. 411-413.
4. Nakamura, H., [A radiographic study of the progression of ossification of the cervical posterior longitudinal ligament: the correlation between the ossification of the posterior longitudinal ligament and that of the anterior longitudinal ligament]. Nippon Seikeigeka Gakkai Zasshi, 1994. 68(9): p. 725-36.
5. Maigne, J.Y., X. AyralH. Guerin-Surville, Frequency and size of ossifications in the caudal attachments of the ligamentum flavum of the thoracic spine. Role of rotatory strains in their development. An anatomic study of 121 spines. Surg Radiol Anat, 1992. 14(2): p. 119-24.
6. Chen, J., X. Wang, C. Wang, et al., Rotational stress: Role in development of ossification of posterior longitudinal ligament and ligamentum flavum. Med Hypotheses, 2010.
7. Tanno, M., K.I. Furukawa, K. Ueyama, et al., Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003. 33(4): p. 475-84.
8. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004. 74(5): p. 448-57.
9. Iwasawa, T., K. Iwasaki, T. Sawada, et al., Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Tissue Int, 2006. 79(6): p. 422-30.
10. Sawada, T., M. Kishiya, K. Kanemaru, et al., Possible role of extracellular nucleotides in ectopic ossification of human spinal ligaments. J Pharmacol Sci, 2008. 106(1): p. 152-61.
11.戴力扬,激素和生长因子在脊柱韧带骨化发生机制中的作用.上海第二医科大学学报, 2004. 24(2): p. 143-146.
12.孔清泉,脊柱韧带骨化相关的易感基因研究进展.中华外科杂志, 2007. 45(20): p. 1435-1437.
13. Terayama, K., Genetic studies on ossification of the posterior longitudinal ligament of the spine. Spine(Phila Pa 1976), 1989. 14(11): p. 1184-91.
14. Ikegawa, S., [Updates on ossification of posterior longitudinal ligament. Genetic approach to the susceptibility genes for ossification of posterior longitudinal ligament of the spine (OPLL) and for its molecular pathogenesis]. Clin Calcium, 2009. 19(10): p. 1457-61.
15. Koga, H., T. Sakou, E. Taketomi, et al., Genetic mapping of ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet, 1998. 62(6): p. 1460-7.
16. Matsunaga, S., [Updates on ossification of posterior longitudinal ligament. Epidemiology and pathogenesis of OPLL]. Clin Calcium, 2009. 19(10): p. 1415-20.
17. Sakou, T., E. Taketomi, S. Matsunaga, et al., Genetic study of ossification of the posterior longitudinal ligament in the cervical spine with human leukocyte antigen haplotype. Spine (Phila Pa 1976), 1991. 16(11): p. 1249-52.
18.刘洋,脊柱后纵韧带骨化性疾病的基础研究进展.脊柱外科杂志, 2010. 8(2): p. 120-123.
19. Tsukahara, S., N. Miyazawa, H. Akagawa, et al., COL6A1, the candidate gene for ossification of the posterior longitudinal ligament, is associated with diffuse idiopathic skeletal hyperostosis in Japanese. Spine (Phila Pa 1976), 2005. 30(20): p. 2321-4.
20. Kim, T.J., T.H. Kim, J.B. Jun, et al., Prevalence of ossification of posterior longitudinal ligament in patients with ankylosing spondylitis. J Rheumatol, 2007. 34(12): p. 2460-2.
21. Hori T, K.Y., Kimura T., How does the ossification area of the posterior longitudinal ligament progress after cervical laminoplasty? Spine (Phila Pa 1976). , 2006. 31(24): p. 2807-12.
22. Matsunaga, S., H. Koga, N. Kawabata, et al., Ossification of the posterior longitudinal ligament in dizygotic twins with schizophrenia: a case report. Mod Rheumatol, 2008. 18(3): p. 277-80.
23.王冰,吴燕红,杨志等, MAPK/ERK信号转导通路的分子生物学特征及生物效应.第四军医大学学报, 2005. 26(suppl): p. 18-21.
24. Courchesne WE, K.R., Thorner J., A putative protein kinase overcomes comes pheromome-induced arrest of cell cycling in S.cerevisiae. cell, 1989. 58: p. 1107一1119.
25. Boulton, T.G., S.H. Nye, D.J. Robbins, et al., ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. cell, 1991. 65(4): p. 663-75.
26. Cobb, M.H., D.J. RobbinsT.G. Boulton, ERKs, extracellular signal-regulated MAP-2 kinases. Curr Opin Cell Biol, 1991. 3(6): p. 1025-32.
27. Widmann, C., S. Gibson, M.B. Jarpe, et al., Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev, 1999. 79(1): p. 143-80.
28. Chang, L.M. Karin, Mammalian MAP kinase signalling cascades. Nature, 2001. 410(6824): p. 37-40.
29. Katso, R.M., O.E. Pardo, A. Palamidessi, et al., Phosphoinositide 3-Kinase C2beta regulatescytoskeletal organization and cell migration via Rac-dependent mechanisms. Mol Biol Cell, 2006. 17(9): p. 3729-44.
30. Katso, R., K. Okkenhaug, K. Ahmadi, et al., Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol, 2001. 17: p. 615-75.
31. Coffey, J.C., J.H. Wang, M.J. Smith, et al., Phosphoinositide 3-kinase accelerates postoperative tumor growth by inhibiting apoptosis and enhancing resistance to chemotherapy-induced apoptosis. Novel role for an old enemy. J Biol Chem, 2005. 280(22): p. 20968-77.
32.孙晓杰,黄常志, PI3K-Akt信号通路与肿瘤.世界华人消化杂志, 2006. 14(3): p. 306-311.
33. Yuan, Z.Q., R.I. Feldman, G.E. Sussman, et al., AKT2 inhibition of cisplatin-induced JNK/p38 and Bax activation by phosphorylation of ASK1: implication of AKT2 in chemoresistance. J Biol Chem, 2003. 278(26): p. 23432-40.
34. Yokoi, K.I.J. Fidler, Hypoxia increases resistance of human pancreatic cancer cells to apoptosis induced by gemcitabine. Clin Cancer Res, 2004. 10(7): p. 2299-306.
35.朱俊峰,不同强度张应力对成骨细胞分化和MAPK磷酸化的影响.上海交通大学博士学位论文, 2009.
36. Furukawa, K., Current topics in pharmacological research on bone metabolism: molecular basis of ectopic bone formation induced by mechanical stress. J Pharmacol Sci, 2006. 100(3): p. 201-4.
1.董军,袁.文,王新伟,等.颈椎后纵韧带骨化成纤维细胞的培养及其生物学特性.脊柱外科杂志, 2007. 5(2): p. 109-112.
2. Tanno, M., K.I. Furukawa, K. Ueyama, et al., Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003. 33(4): p. 475-84.
3. Li, H., D. Liu, C.Q. Zhao, et al., High glucose promotes collagen synthesis by cultured cells from rat cervical posterior longitudinal ligament via transforming growth factor-beta1. Eur Spine J, 2008. 17(6): p. 873-81.
4. Li, H., D. Liu, C.Q. Zhao, et al., Insulin potentiates the proliferation and bone morphogenetic protein-2-induced osteogenic differentiation of rat spinal ligament cells via extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. Spine (Phila Pa 1976), 2008. 33(22): p. 2394-402.
5. Iwasawa, T., K. Iwasaki, T. Sawada, et al., Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Tissue Int, 2006. 79(6): p. 422-30.
6. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004. 74(5): p. 448-57.
1. Tsukamoto, N., T. Maeda, H. Miura, et al., Repetitive tensile stress to rat caudal vertebrae inducing cartilage formation in the spinal ligaments: a possible role of mechanical stress in the development of ossification of the spinal ligaments. J Neurosurg Spine, 2006. 5(3): p. 234-42.
2. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004. 74(5): p. 448-57.
3. Tanno, M., K.I. Furukawa, K. Ueyama, et al., Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003. 33(4): p. 475-84.
4. Qi, J., L. Chi, J. Wang, et al., Modulation of collagen gel compaction by extracellular ATP is MAPK and NF-kappaB pathways dependent. Exp Cell Res, 2009. 315(11): p. 1990-2000.
5. Granet, C., A.G. Vico, C. Alexandre, et al., MAP and src kinases control the induction of AP-1 members in response to changes in mechanical environment in osteoblastic cells. Cell Signal, 2002. 14(8): p. 679-88.
6. Granet, C., N. Boutahar, L. Vico, et al., MAPK and SRC-kinases control EGR-1 and NF-kappa B inductions by changes in mechanical environment in osteoblasts. Biochem Biophys Res Commun, 2001. 284(3): p. 622-31.
7. Jilka, R.L., R.S. Weinstein, T. Bellido, et al., Osteoblast programmed cell death (apoptosis): modulation by growth factors and cytokines. J Bone Miner Res, 1998. 13(5): p. 793-802.
8.刘洋,李刚,李建福,付小兵.细胞机械应力响应的生物学基础及机制研究进展中国美容医学, 2007. 16(3): p. 421-423.
9. Cantiello, H.F., Role of the actin cytoskeleton on epithelial Na+ channel regulation. Kidney Int, 1995. 48(4): p. 970-84.
10. Doyle, A.M., R.M. NeremT. Ahsan, Human mesenchymal stem cells form multicellular structures in response to applied cyclic strain. Ann Biomed Eng, 2009. 37(4): p. 783-93.
11. Molitoris, B.A., Putting the actin cytoskeleton into perspective: pathophysiology of ischemic alterations. Am J Physiol, 1997. 272(4 Pt 2): p. F430-3.
12. Dartsch, P.C.E. Betz, Response of cultured endothelial cells to mechanical stimulation. Basic Res Cardiol, 1989. 84(3): p. 268-81.
13. Wang, J.H., P. Goldschmidt-Clermont, J. Wille, et al., Specificity of endothelial cell reorientation in response to cyclic mechanical stretching. J Biomech, 2001. 34(12): p. 1563-72.
14. Hayakawa, K., N. SatoT. Obinata, Dynamic reorientation of cultured cells and stress fibers under mechanical stress from periodic stretching. Exp Cell Res, 2001. 268(1): p. 104-14.
15. Sanchez-Esteban, J., Y. Wang, L.A. Cicchiello, et al., Cyclic mechanical stretch inhibits cell proliferation and induces apoptosis in fetal rat lung fibroblasts. Am J Physiol Lung Cell Mol Physiol, 2002. 282(3): p. L448-56.
16. Kobayashi, Y., F. Hashimoto, H. Miyamoto, et al., Force-induced osteoclast apoptosis in vivo is accompanied by elevation in transforming growth factor beta and osteoprotegerin expression. J Bone Miner Res, 2000. 15(10): p. 1924-34.
1. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004. 74(5): p. 448-57.
2. Tanno, M., K.I. Furukawa, K. Ueyama, et al., Uniaxial cyclic stretch induces osteogenicdifferentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003. 33(4): p. 475-84.
3. Trieb, K., H. BlahovecB. Kubista, Effects of hyperthermia on heat shock protein expression, alkaline phosphatase activity and proliferation in human osteosarcoma cells. Cell Biochem Funct, 2007. 25(6): p. 669-72.
4. Oyajobi, B.O., I.R. Garrett, A. Gupta, et al., Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease. Br J Haematol, 2007. 139(3): p. 434-8.
5. Fukumoto, S., [PTH and mechanical stress]. Clin Calcium, 2008. 18(9): p. 1327-31.
6. Jiang, J.X., A.J. Siller-JacksonS. Burra, Roles of gap junctions and hemichannels in bone cell functions and in signal transmission of mechanical stress. Front Biosci, 2007. 12: p. 1450-62.
7. Sawada, T., M. Kishiya, K. Kanemaru, et al., Possible role of extracellular nucleotides in ectopic ossification of human spinal ligaments. J Pharmacol Sci, 2008. 106(1): p. 152-61.
8. Iwasawa, T., K. Iwasaki, T. Sawada, et al., Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Tissue Int, 2006. 79(6): p. 422-30.
9. Ito, Y.Y.W. Zhang, A RUNX2/PEBP2alphaA/CBFA1 mutation in cleidocranial dysplasia revealing the link between the gene and Smad. J Bone Miner Metab, 2001. 19(3): p. 188-94.
10. Thirunavukkarasu, K., M. Mahajan, K.W. McLarren, et al., Two domains unique to osteoblast-specific transcription factor Osf2/Cbfa1 contribute to its transactivation function and its inability to heterodimerize with Cbfbeta. Mol Cell Biol, 1998. 18(7): p. 4197-208.
11. Xiao, Z.S., L.G. SimpsonL.D. Quarles, IRES-dependent translational control of Cbfa1/Runx2 expression. J Cell Biochem, 2003. 88(3): p. 493-505.
12. Ducy, P., R. Zhang, V. Geoffroy, et al., Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell, 1997. 89(5): p. 747-54.
1. Ziros, P.G., A.P. Gil, T. Georgakopoulos, et al., The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells. J Biol Chem, 2002. 277(26): p. 23934-41.
2. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament.Calcif Tissue Int, 2004. 74(5): p. 448-57.
3. Xiao, G., D. Jiang, P. Thomas, et al., MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J Biol Chem, 2000. 275(6): p. 4453-9.
4. Kanno, T., T. Takahashi, T. Tsujisawa, et al., Mechanical stress-mediated Runx2 activation is dependent on Ras/ERK1/2 MAPK signaling in osteoblasts. J Cell Biochem, 2007. 101(5): p. 1266-77.
5. Granet, C., A.G. Vico, C. Alexandre, et al., MAP and src kinases control the induction of AP-1 members in response to changes in mechanical environment in osteoblastic cells. Cell Signal, 2002. 14(8): p. 679-88.
6. Liu, L., W. YuanJ. Wang, Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress. Biomech Model Mechanobiol, 2010.
7. Danciu, T.E., R.M. Adam, K. Naruse, et al., Calcium regulates the PI3K-Akt pathway in stretched osteoblasts. FEBS Lett, 2003. 536(1-3): p. 193-7.
8. Lee, D.Y., Y.S. Li, S.F. Chang, et al., Oscillatory flow-induced proliferation of osteoblast-like cells is mediated by alphavbeta3 and beta1 integrins through synergistic interactions of focal adhesion kinase and Shc with phosphatidylinositol 3-kinase and the Akt/mTOR/p70S6K pathway. J Biol Chem, 2010. 285(1): p. 30-42.
9. Lin, T.H., C.H. Tang, S.Y. Hung, et al., Upregulation of heme oxygenase-1 inhibits the maturation and mineralization of osteoblasts. J Cell Physiol, 2010. 222(3): p. 757-68.
10. Olkku, A., J.J. Leskinen, M.J. Lammi, et al., Ultrasound-induced activation of Wnt signaling in human MG-63 osteoblastic cells. Bone, 2010. 47(2): p. 320-30.
11. Triplett, J.W., R. O'Riley, K. Tekulve, et al., Mechanical loading by fluid shear stress enhances IGF-1 receptor signaling in osteoblasts in a PKCzeta-dependent manner. Mol Cell Biomech, 2007. 4(1): p. 13-25.
12. Takai, S., H. Tokuda, Y. Hanai, et al., Activation of phosphatidylinositol 3-kinase/Akt limits FGF-2-induced VEGF release in osteoblasts. Mol Cell Endocrinol, 2007. 267(1-2): p. 46-54.
13. Norvell, S.M., M. Alvarez, J.P. Bidwell, et al., Fluid shear stress induces beta-catenin signaling in osteoblasts. Calcif Tissue Int, 2004. 75(5): p. 396-404.
14. Chang, E.J., H.H. Kim, J.E. Huh, et al., Low proliferation and high apoptosis of osteoblastic cells on hydrophobic surface are associated with defective Ras signaling. Exp Cell Res, 2005. 303(1): p. 197-206.
15. Xia, X., N. Batra, Q. Shi, et al., Prostaglandin promotion of osteocyte gap junction function through transcriptional regulation of connexin 43 by glycogen synthase kinase 3/beta-catenin signaling. Mol Cell Biol, 2010. 30(1): p. 206-19.
16. Li, H., D. Liu, C.Q. Zhao, et al., Insulin potentiates the proliferation and bone morphogenetic protein-2-induced osteogenic differentiation of rat spinal ligament cells via extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. Spine (Phila Pa 1976), 2008. 33(22): p. 2394-402.
1. Nakamura, H., [A radiographic study of the progression of ossification of the cervical posterior longitudinal ligament: the correlation between the ossification of the posterior longitudinal ligament and that of the anterior longitudinal ligament]. Nippon Seikeigeka Gakkai Zasshi, 1994. 68(9): p. 725-36.
2. Tsukamoto, N., T. Maeda, H. Miura, et al., Repetitive tensile stress to rat caudal vertebrae inducing cartilage formation in the spinal ligaments: a possible role of mechanical stress in the development of ossification of the spinal ligaments. J Neurosurg Spine, 2006. 5(3): p. 234-42.
3. Tanno, M., K.I. Furukawa, K. Ueyama, et al., Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003. 33(4): p. 475-84.
4. Iwasaki, K., K.I. Furukawa, M. Tanno, et al., Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004. 74(5): p. 448-57.
5. Iwasawa, T., K. Iwasaki, T. Sawada, et al., Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Tissue Int, 2006. 79(6): p. 422-30.
6. Sawada, T., M. Kishiya, K. Kanemaru, et al., Possible role of extracellular nucleotides in ectopic ossification of human spinal ligaments. J Pharmacol Sci, 2008. 106(1): p. 152-61.
7.戴力扬,激素和生长因子在脊柱韧带骨化发生机制中的作用.上海第二医科大学学报, 2004. 24(2): p. 143-146.
8.孔清泉,脊柱韧带骨化相关的易感基因研究进展.中华外科杂志, 2007. 45(20): p. 1435-1437.
9. Terayama, K., Genetic studies on ossification of the posterior longitudinal ligament of the spine. Spine (Phila Pa 1976), 1989. 14(11): p. 1184-91.
10. Ikegawa, S., [Updates on ossification of posterior longitudinal ligament. Genetic approach to the susceptibility genes for ossification of posterior longitudinal ligament of the spine (OPLL) and for its molecular pathogenesis]. Clin Calcium, 2009. 19(10): p. 1457-61.
11. Koga, H., T. Sakou, E. Taketomi, et al., Genetic mapping of ossification of the posterior longitudinal ligament of the spine. Am J Hum Genet, 1998. 62(6): p. 1460-7.
12. Matsunaga, S., [Updates on ossification of posterior longitudinal ligament. Epidemiology and pathogenesis of OPLL]. Clin Calcium, 2009. 19(10): p. 1415-20.
13. Tsukahara, S., N. Miyazawa, H. Akagawa, et al., COL6A1, the candidate gene for ossification of the posterior longitudinal ligament, is associated with diffuse idiopathic skeletal hyperostosis in Japanese. Spine (Phila Pa 1976), 2005. 30(20): p. 2321-4.
14. Kim, T.J., T.H. Kim, J.B. Jun, et al., Prevalence of ossification of posterior longitudinal ligament in patients with ankylosing spondylitis. J Rheumatol, 2007. 34(12): p. 2460-2.
15. Hori T, K.Y., Kimura T., How does the ossification area of the posterior longitudinal ligament progress after cervical laminoplasty? Spine (Phila Pa 1976). , 2006. 31(24): p. 2807-12.
16. Matsunaga, S., H. Koga, N. Kawabata, et al., Ossification of the posterior longitudinal ligament in dizygotic twins with schizophrenia: a case report. Mod Rheumatol, 2008. 18(3): p. 277-80.
17. Danciu, T.E., R.M. Adam, K. Naruse, et al., Calcium regulates the PI3K-Akt pathway in stretchedosteoblasts. FEBS Lett, 2003. 536(1-3): p. 193-7.
18. Lee, D.Y., Y.S. Li, S.F. Chang, et al., Oscillatory flow-induced proliferation of osteoblast-like cells is mediated by alphavbeta3 and beta1 integrins through synergistic interactions of focal adhesion kinase and Shc with phosphatidylinositol 3-kinase and the Akt/mTOR/p70S6K pathway. J Biol Chem, 2010. 285(1): p. 30-42.
19. Lin, T.H., C.H. Tang, S.Y. Hung, et al., Upregulation of heme oxygenase-1 inhibits the maturation and mineralization of osteoblasts. J Cell Physiol, 2010. 222(3): p. 757-68.
20. Olkku, A., J.J. Leskinen, M.J. Lammi, et al., Ultrasound-induced activation of Wnt signaling in human MG-63 osteoblastic cells. Bone, 2010. 47(2): p. 320-30.
21. Triplett, J.W., R. O'Riley, K. Tekulve, et al., Mechanical loading by fluid shear stress enhances IGF-1 receptor signaling in osteoblasts in a PKCzeta-dependent manner. Mol Cell Biomech, 2007. 4(1): p. 13-25.
22. Takai, S., H. Tokuda, Y. Hanai, et al., Activation of phosphatidylinositol 3-kinase/Akt limits FGF-2-induced VEGF release in osteoblasts. Mol Cell Endocrinol, 2007. 267(1-2): p. 46-54.
23. Norvell, S.M., M. Alvarez, J.P. Bidwell, et al., Fluid shear stress induces beta-catenin signaling in osteoblasts. Calcif Tissue Int, 2004. 75(5): p. 396-404.
24. Chang, E.J., H.H. Kim, J.E. Huh, et al., Low proliferation and high apoptosis of osteoblastic cells on hydrophobic surface are associated with defective Ras signaling. Exp Cell Res, 2005. 303(1): p. 197-206.
25. Xia, X., N. Batra, Q. Shi, et al., Prostaglandin promotion of osteocyte gap junction function through transcriptional regulation of connexin 43 by glycogen synthase kinase 3/beta-catenin signaling. Mol Cell Biol, 2010. 30(1): p. 206-19.
1贾连顺.颈椎后纵韧带骨化并不都需要手术.中国矫形外科杂志, 2009; 17(7):481
2 Kim TJ, Bae KW, Uhm WS, et al. Prevalence of ossification of the posterior longitudinal ligament of the cervical spine. Joint Bone Spine, 2008; 75(4):471-474
3 Hirabayashi K, Miyakawa J, Satomi K, et al. Operative results and postoperative progression of ossification among patients with ossification of cervical posterior longitudinal ligament. Spine(Phila Pa 1976), 1981; 6(4):354-364
4 Epstein NE. Ossification of the posterior longitudinal ligament in evolution in 12 patients. Spine(Phila Pa 1976), 1994; 19(6):673-701
5 Murakami M, Seichi A, Chikuda H, et al. Long-term follow-up of the progression of ossification of the posterior longitudinal ligament. J Neurosurg Spine, 2010; 12(5):577-579
6 Honda H. Histopathological study of aging of the posterior portion of human cervical vertebral bodies and discs with special reference to the early ossification of the posterior longitudinal ligament. Nippon Seikeigeka Gakkai Zasshi, 1983; 57(12):1881-1893
7 Ono K, Yonenobu K, Miyamoto S, et al. Pathology of ossification of the posterior longitudinal ligament and ligamentum flavum. Clin Orthop Relat Res, 1999; 359:18-26
8 Yoshizawa T, Naitoh Y, Yoshida M, et al. Cervical myelopathy due to hypertrophy of the posterior longitudinal ligament (HPLL): a case report. Rinsho Shinkeigaku, 1991; 31(7):720-724
9 Mizuno J, Nakagawa H, Hashizume Y. Myelopathy caused by hypertrophy of the posterior longitudinal ligament of the cervical spine in a patient with long-term hemodialysis. No Shinkei Geka, 1996; 24(7):655-659
10 Song J, Mizuno J, Hashizume Y, et al. Immunohistochemistry of symptomatic hypertrophy of the posterior longitudinal ligament with special reference to ligamentous ossification. Spinal Cord, 2006; 44(9):576-581
11戴力扬.激素和生长因子在脊柱韧带骨化发生机制中的作用.上海第二医科大学学报, 2004; 24(2):143-146
12 Kobashi G, Ohta K, Washio M, et al. FokI variant of vitamin D receptor gene and factors related to atherosclerosis associated with ossification of the posterior longitudinal ligament of the spine: a multi-hospital case-control study. Spine(Phila Pa 1976), 2008; 33(16):E553-E558
13 Ito K, Matsuyama Y, Yukawa Y, et al. Analysis of interleukin-8, interleukin-10, and tumor necrosis factor-alpha in the cerebrospinal fluid of patients with cervical spondylotic myelopathy. J Spinal Disord Tech, 2008; 21(2):145-147
14 Kishiya M, Sawada T, Kanemaru K, et al. A functional RNAi screen for Runx2-regulated genes associated with ectopic bone formation in human spinal ligaments. J Pharmacol Sci, 2008; 106(3):404-414
15 Li H, Liu D, Zhao CQ, et al. Insulin potentiates the proliferation and bone morphogenetic protein-2-induced osteogenic differentiation of rat spinal ligament cells via extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. Spine(Phila Pa 1976), 2008; 33(22):2394-2402
16 Li H, Liu D, Zhao CQ, et al. High glucose promotes collagen synthesis by cultured cells from rat cervical posterior longitudinal ligament via transforming growth factor-beta1. Eur Spine J, 2008; 17(6):873-881
17 Eun JP, Ma TZ, Lee WJ, et al. Comparative analysis of serum proteomes to discover biomarkers for ossification of the posterior longitudinal ligament. Spine(Phila Pa 1976), 2007; 32(7):728-734
18张颖.颈椎后纵韧带骨化症发病机制的比较蛋白组学研究[D].第二军医大学博士学位论文, 2008
19 Nakamura H. A radiographic study of the progression of ossification of the cervical posterior longitudinal ligament: the correlation between the ossification of the posterior longitudinal ligament and that of the anterior longitudinal ligament. Nippon Seikeigeka Gakkai Zasshi, 1994; 68(9):725-736
20 Tsukamoto N, Maeda T, Miura H, et al. Repetitive tensile stress to rat caudal vertebrae inducing cartilage formation in the spinal ligaments: a possible role of mechanical stress in the development of ossification of the spinal ligaments. J Neurosurg Spine, 2006; 5(3):234-242
21 Miyazawa N, Akiyama I. Ossification of the ligamentum flavum of the cervical spine. J Neurosurg Sci, 2007; 51(3):139-144
22谭炳毅,贾连顺,王海燕,等.应力刺激对于后纵韧带骨化因子的影响.中国矫形外科杂志, 2006; 14(13):1013-1015
23向选平,金涛,王华,等.手术刺激对腰椎后纵韧带内BMP-2及BMP-7 mRNA表达的影响.中国现代医学杂志, 2010; 20(6):858-864
24 Maigne JY, Ayral X, Guerin-Surville H. Frequency and size of ossifications in the caudal attachments of theligamentum flavum of the thoracic spine. Role of rotatory strains in their development. An anatomic study of 121 spines. Surg Radiol Anat, 1992; 14(2):119-124
25 Chen J, Wang X, Wang C, et al. Rotational stress: Role in development of ossification of posterior longitudinal ligament and ligamentum flavum. Med Hypotheses, 2010;[Epub ahead of print]
26 Tanno M, Furukawa KI, Ueyama K, et al. Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003; 33(4):475-484
27 Iwasaki K, Furukawa KI, Tanno M, et al. Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int, 2004; 74(5):448-457
28 Iwasawa T, Iwasaki K, Sawada T, et al. Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Tissue Int, 2006; 79(6):422-430
29 Sawada T, Kishiya M, Kanemaru K, et al. Possible role of extracellular nucleotides in ectopic ossification of human spinal ligaments. J Pharmacol Sci, 2008; 106(1):152-161
30 Azuma Y, Kato Y, Taguchi T. Etiology of cervical myelopathy induced by ossification of the posterior longitudinal ligament: determining the responsible level of OPLL myelopathy by correlating static compression and dynamic factors. J Spinal Disord Tech, 2010; 23(3):166-169
31 Fujiyoshi T, Yamazaki M, Okawa A, et al. Static versus dynamic factors for the development of myelopathy in patients with cervical ossification of the posterior longitudinal ligament. J Clin Neurosci, 2010; 17(3):320-324
32 Kato Y, Kanchiku T, Imajo Y, et al. Biomechanical study of the effect of degree of static compression of the spinal cord in ossification of the posterior longitudinal ligament. J Neurosurg Spine, 2010; 12(3):301-305
33 Nakae R, Onda H, Yokobori S, et al. Clinical analysis of spinal cord injury with or without cervical ossification of the posterior longitudinal ligament, spondylosis, and canal stenosis in elderly head injury patients. Neurol Med Chir(Tokyo), 2010; 50(6):461-465
34 Yoo DS, Lee SB, Huh PW, et al. Spinal cord injury in cervical spinal stenosis by minor trauma. World Neurosurg, 2010; 73(1):50-52
35 Sugimoto Y, Ito Y, Tanaka M, et al. Cervical cord injury in patients with ankylosed spines: progressive paraplegia in two patients after posterior fusion without decompression. Spine(Phila Pa 1976), 2009; 34(23):E861-E863
36 Tsukahara S, Miyazawa N, Akagawa H, et al. COL6A1, the candidate gene for ossification of the posterior longitudinal ligament, is associated with diffuse idiopathic skeletal hyperostosis in Japanese. Spine (Phila Pa 1976), 2005; 30(20):2321-2324
37 Kim TJ, Kim TH, Jun JB, et al. Prevalence of ossification of posterior longitudinal ligament in patients with ankylosing spondylitis. J Rheumatol, 2007; 34(12):2460-2462
38 Hori T, Kawaguchi Y, Kimura T. How does the ossification area of the posterior longitudinal ligament progress after cervical laminoplasty Spine(Phila Pa 1976), 2006; 31(24):2807-2812
39 Matsunaga S, Koga H, Kawabata N, et al. Ossification of the posterior longitudinal ligament in dizygotic twins with schizophrenia: a case report. Mod Rheumatol, 2008; 18(3):277-280
[1] Matsunaga S., Sakou T., Taketomi E., et al. The natural course of myelopathy caused by ossification of the posterior longitudinal ligament in the cervical spine. Clin Orthop Relat Res,1994; (305):168-77.
[2] Miyazawa N., Akiyama I. Ossification of the ligamentum flavum of the cervical spine. J Neurosurg Sci,2007; 51(3):139-44.
[3]秦德安,李晓东,崔新刚,刘峰.胸椎椎板倾斜角在胸椎黄韧带骨化中的解剖学意义.中国临床解剖学杂志,2006; 24(6):634-636.
[4] Chen Y., Lu X. H., Yang L. L., et al. Ossification of ligamentum flavum related to thoracic kyphosis after tuberculosis: case report and review of the literature. Spine (Phila Pa 1976),2009; 34(1):E41-4.
[5] Maigne J. Y., Ayral X., Guerin-Surville H. Frequency and size of ossifications in the caudal attachments of the ligamentum flavum of the thoracic spine. Role of rotatory strains in their development. An anatomic study of 121 spines. Surg Radiol Anat,1992; 14(2):119-24.
[6] Chen J., Wang X., Wang C., et al. Rotational stress: Role in development of ossification of posterior longitudinal ligament and ligamentum flavum. Med Hypotheses,2010.
[7] Hale J. J., Gruson K. I., Spivak J. M. Laminoplasty: a review of its role in compressive cervical myelopathy. Spine J,2006; 6(6 Suppl):289S-298S.
[8] Sugimoto Y., Ito Y., Tanaka M., et al. Cervical cord injury in patients with ankylosed spines: progressive paraplegia in two patients after posterior fusion without decompression. Spine (Phila Pa 1976),2009; 34(23):E861-3.
[9] Takatsu T., Ishida Y., Suzuki K., et al. Radiological study of cervical ossification of the posterior longitudinal ligament. J Spinal Disord,1999; 12(3):271-3.
[10] Hirabayashi K., Miyakawa J., Satomi K., et al. Operative results and postoperative progression ofossification among patients with ossification of cervical posterior longitudinal ligament. Spine (Phila Pa 1976),1981; 6(4):354-64.
[11] Nakamura H. [A radiographic study of the progression of ossification of the cervical posterior longitudinal ligament: the correlation between the ossification of the posterior longitudinal ligament and that of the anterior longitudinal ligament]. Nippon Seikeigeka Gakkai Zasshi,1994; 68(9):725-36.
[12] Kawaguchi Y., Kanamori M., Ishihara H., et al. Progression of ossification of the posterior longitudinal ligament following en bloc cervical laminoplasty. J Bone Joint Surg Am,2001; 83-A(12):1798-802.
[13] Tokuhashi Y., Ajiro Y., Umezawa N. A patient with two re-surgeries for delayed myelopathy due to progression of ossification of the posterior longitudinal ligaments after cervical laminoplasty. Spine (Phila Pa 1976),2009; 34(2):E101-5.
[14] Li F., Chen Q., Xu K. Surgical treatment of 40 patients with thoracic ossification of the ligamentum flavum. J Neurosurg Spine,2006; 4(3):191-7.
[15] Wang W., Kong L. Ossification of ligamentum. J Neurosurg Spine,2007; 6(1):96; author reply 96-7.
[16] Tateiwa Y., Kamimura M., Itoh H., et al. Multilevel subtotal corpectomy and interbody fusion using a fibular bone graft for cervical myelopathy due to ossification of the posterior longitudinal ligament. J Clin Neurosci,2003; 10(2):199-207.
[17] Furusawa N., Baba H., Imura S., et al. Characteristics and mechanism of the ossification of posterior longitudinal ligament in the tip-toe walking Yoshimura (twy) mouse. Eur J Histochem,1996; 40(3):199-210.
[18] Tsukamoto N., Maeda T., Miura H., et al. Repetitive tensile stress to rat caudal vertebrae inducing cartilage formation in the spinal ligaments: a possible role of mechanical stress in the development of ossification of the spinal ligaments. J Neurosurg Spine,2006; 5(3):234-42.
[19]谭炳毅;贾连顺;王海燕;蔡国栋;董军;.应力刺激对于后纵韧带骨化因子的影响.中国矫形外科杂志,2006; 13.
[20]向选平,金涛,王华等.手术刺激对腰椎后纵韧带内BMP-2及BMP-7 mRNA表达的影响.中国现代医学杂志,2010; 20(6):858-864.
[21] Tanno M., Furukawa K. I., Ueyama K., et al. Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone,2003; 33(4):475-84.
[22] Iwasaki K., Furukawa K. I., Tanno M., et al. Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. Calcif Tissue Int,2004; 74(5):448-57.
[23] Iwasawa T., Iwasaki K., Sawada T., et al. Pathophysiological role of endothelin in ectopic ossification ofhuman spinal ligaments induced by mechanical stress. Calcif Tissue Int,2006; 79(6):422-30.
[24] Ohishi H., Furukawa K., Iwasaki K., et al. Role of prostaglandin I2 in the gene expression induced by mechanical stress in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. J Pharmacol Exp Ther,2003; 305(3):818-24.
[25]杨海松. Connexin43在机械应力诱导颈椎后纵韧带骨化进展过程中的作用研究[D].第二军医大学,2010.