辐射肾性骨病病理特点与细胞分子机制研究
|
摘要
目的 肾脏损伤是腹部肿瘤放疗不可忽视的并发症之一,射线致肾脏损伤称为辐射性肾病(radiation nephropathy),其病理特点与发生机制并未完全阐明。肾功能异常导致的骨代谢障碍称为肾性骨病(renal osteodystrophy),其病理表现多样,发生机制复杂。本研究拟通过直接照射建立大鼠肾辐射损伤模型,并用原代培养肾小管上皮细胞和成骨细胞的方法研究肾脏、骨骼的病理特点与细胞分子机制,为辐射性肾病和肾性骨病的防治提供实验依据。
方法 应用15Gy 137Cs-γ射线照射大鼠肾脏的方法制备肾辐射损伤模型,并以肾大部切除和手术不照射为对照。放免、酶免、自动生化分析仪等方法测定血尿生化指标。光镜及电镜观察肾脏和骨骼的病理改变。测定腰椎和股骨的骨密度和干重、灰重,并进行骨组织形态计量学分析,测定腰椎和股骨的骨生物力学性能。RT-PCR法检测肾脏TGF-β、OPN、IGF-I、COL-I、VDR、1α羟化酶、24羟化酶mRNA表达,骨骼TGF-β、OPN、IGF-I、COL-I、VDR、OPG、RANKL表达,Western blot法检测肾脏TGF-β、OPN、IGF-I蛋白表达改变。体外培养肾小管上皮细胞,观察1Gy、5Gy、10Gyγ射线照射及PTH(1～34)和25(OH)D3对其增殖和功能的影响。观察受1Gy、5Gy、10Gyγ射线照射后的肾小管上皮细胞培养上清液对体外培养成骨细胞增殖和功能的调节作用,以及TGF-β中和抗体、IGF-I中和抗体和OPN中和抗体对肾小管上皮细胞培养上清液对成骨细胞调节作用的影响。
结果 15Gy 137Cs-γ射线肾局部照射可致肾功能尤其是肾小管功能的进行性减退。肾脏体积缩小,肾小球肿大,Bowman氏囊囊腔狭窄甚至消失,部分肾小管上皮细胞变性、坏死,线粒体肿胀,线粒体嵴变短、减少、排列紊乱,肾间质出现明显的进行性纤维化;肾TGF-β1的mRNA和蛋白质表达量增加;肾1α羟化酶、24羟化酶、VDR mRNA表达量明显下降。股骨干重、灰重、腰椎和股骨BMD明显降低,胫骨和腰椎骨小梁体积、骨小梁宽度、骨小梁数减少,骨小梁间距增加,胫骨骨吸收表面、MAR增大;骨组织TGF-β1、IGF-I、OPN mRNA表达升高,RANKL/OPG比例升高;腰椎压缩和股骨三点弯最大载荷明显降低;血PTH、ALP、尿Pyd / Cr显著升高,血1α,25(OH)2D3显著降低。萌格旺治疗组肾功能和组织结构无显著改善,但血1,25(OH)2D3升高、尿Pyd / Cr降低、骨吸收表面降低、骨量提高、生物力学性能改善。1Gy、5Gy、10Gyγ射线照射后肾小管上皮细胞增
殖能力降低,细胞数减少,1α羟化酶、24羟化酶mRNA 表达降低,TGF-βmRNA表达增高。PTH(1～34)可显著抑制肾小管上皮细胞增殖,促进1α羟化酶基因表达,抑制24羟化酶基因表达,而25(OH)D3对肾小管上皮细胞增殖的影响较小,可促进24羟化酶的表达,而抑制1α羟化酶基因表达。正常肾小管上皮细胞培养上清液可促进成骨细胞增殖、分化和相关基因mRNA表达,降低RANKL/OPG比值,提高碱性磷酸酶活性和矿化结节形成率。受不同剂量射线照射后的肾小管上皮细胞培养上清液对成骨细胞增殖、基因表达和矿化功能的促进作用降低,且剂量越高,作用越弱。抗TGF-β抗体、抗IGF-I抗体和抗OPN抗体均可部分影响肾小管上皮细胞对成骨细胞增殖和功能的调节作用。
结论 (1)15Gy 137Cs-γ射线局部照射大鼠肾脏引起肾组织病理和肾功能进行性损伤;(2)肾辐射损伤诱发明显的骨结构破坏、骨量减少、生物力学性能降低,呈骨转换加速的病理特点;(3)肾辐射骨损伤的主要机制是肾1α羟化酶活性下调致活性维生素D合成障碍,并出现继发性PTH升高,导致骨代谢失平衡;(4)1Gy、5Gy、10Gy γ射线可导致肾小管上皮细胞增殖和功能的降低;(5)肾小管上皮细胞培养上清液对成骨细胞增殖和功能有促进作用,可能是骨重建调节机制之一;(6)TGF-β、IGF-I、OPN参与肾小管上皮细胞对成骨细胞增殖和功能的调节。
Objective Renal injury induced by abdomen radio-therapy, known as radiation nephropathy, is one of the serious complications of this therapy. The pathological characteristics and mechanisms of radiation nephropathy have not been fully understood. Renal osteodystrophy is characterized by various in pathological representations and mechanisms. The present study has established a rat model of renal osteodystrophy by directly irradiation of both kidneys with γ rays. Meanwhile, the primary renal tubule cells and osteoblasts were used to study the pathological characteristics of kidney and bone as well as the possible cellular molecular mechanisms of this disease. By doing so, it is hoped to provide some useful information for preventing and therapy of this disease.
Methods Rat model of irradiation-induced renal injury was established by subjecting both kidneys to 15 Gy Cs137 γ-rays after surgical exposure. 5/6 nephrectomy model was used as compare. Serum and urinal parameters were analyzed by means of RIA, MIA and autoanalyzer. Pathological characteristics of kidneys and bones were studied by light microscope, SEM and TEM. Bone mineral density of lumbar and femurs were determined by DEXA and physical density detector. The dry weight and ash weight of lumbar and femurs were measured. Decalcified slides of lumbar and un-decalcified slides of tibia were made for bone histomorphometry. Biomechanical property of lumbar and femurs were also detected. The mRNA level of TGF-β,OPN,IGF-I,COL-I,VDR,1α-hydroxylase and 24- hydroxylase in the kidney and of TGF-β,OPN,IGF-I,COL-I,VDR,OPG and RANKL in the bone were determined by RT-PCR. The protein level of TGF-β,OPN,IGF-I was determined by Western blot. Primary renal tubule
epithelial cells were subjected to 1Gy,5Gy,10Gy γ rays, as well as to PTH(1～34) and 25(OH)D3.The effects of these factors on proliferation and function of renal tubule epithelial cells were studied. Finally, the effects of culture medium of renal tubule epithelial cells on proliferation and function of primary osteoblasts were studied.
Results Irradiation of both kidneys with 15 Gy Cs137 γ-rays resulted in progressive letdown of renal function, especially of tubule function. The pathological exhibition includes reducing in mass, swell of glomerular, that Bowman’s capsules straitened or disappeared, and some epithelia denaturalized or died. The Mitochondria of tubule epithelial cells were tumefied and the cristae were shortened, lessened and disordered. Progressive fibrosis in renal matrix was found. The mRNA and protein level of TGF-β1 were augmented. The mRNA level of 1α-hydroxylase,24 –hydroxylase and VDR was decreased. The dry weight and ash weight, BMD of femur and lumbar were significantly reduced. TV/BV,Tb.Th,Tb.N of tibia and lumbar were distinctly decreased and Tb.Sp was increased. The mRNA level of TGF-β1,IGF-I,OPN in bone was increased, and the ratio of RANKL/OPG was increased. The maximum load of lumbar and femur were significantly reduced. In the serum, PTH,total ALP were increased and 1,25(OH)2D3 was significantly decreased. The Pyd/Cr in urine was increased. Treating rat with BONE-ONE after irradiation had little effect on renal function and structure, but could result in increasing in bone mass and bone biomechanical property. Irradiation of renal tubule cells with 1Gy,5Gy,10Gyγ-rays resulted in decreasing in proliferation and cell number. The mRNA level of 1α-hydroxylase and 24 –hydroxylase were also reduced, while TGF-βmRNA level was increased. PTH(1～34) significantly suppressed proliferation of tubule epithelial cells, while promoted expression of 1α-hydroxylase and suppressed expression of 24-hydroxylase. 25(OH)D3 had little effect on proliferation of tubule epithelial cells, but promoted expression of 24-hydroxylase and suppressed expression of 1α-hydroxylase. The culture medium of renal tubule epithelial cells significantly promoted proliferation and differentiation of osteoblasts, enhanced expression of related genes (and),
reduced the ratio
方法 应用15Gy 137Cs-γ射线照射大鼠肾脏的方法制备肾辐射损伤模型,并以肾大部切除和手术不照射为对照。放免、酶免、自动生化分析仪等方法测定血尿生化指标。光镜及电镜观察肾脏和骨骼的病理改变。测定腰椎和股骨的骨密度和干重、灰重,并进行骨组织形态计量学分析,测定腰椎和股骨的骨生物力学性能。RT-PCR法检测肾脏TGF-β、OPN、IGF-I、COL-I、VDR、1α羟化酶、24羟化酶mRNA表达,骨骼TGF-β、OPN、IGF-I、COL-I、VDR、OPG、RANKL表达,Western blot法检测肾脏TGF-β、OPN、IGF-I蛋白表达改变。体外培养肾小管上皮细胞,观察1Gy、5Gy、10Gyγ射线照射及PTH(1～34)和25(OH)D3对其增殖和功能的影响。观察受1Gy、5Gy、10Gyγ射线照射后的肾小管上皮细胞培养上清液对体外培养成骨细胞增殖和功能的调节作用,以及TGF-β中和抗体、IGF-I中和抗体和OPN中和抗体对肾小管上皮细胞培养上清液对成骨细胞调节作用的影响。
结果 15Gy 137Cs-γ射线肾局部照射可致肾功能尤其是肾小管功能的进行性减退。肾脏体积缩小,肾小球肿大,Bowman氏囊囊腔狭窄甚至消失,部分肾小管上皮细胞变性、坏死,线粒体肿胀,线粒体嵴变短、减少、排列紊乱,肾间质出现明显的进行性纤维化;肾TGF-β1的mRNA和蛋白质表达量增加;肾1α羟化酶、24羟化酶、VDR mRNA表达量明显下降。股骨干重、灰重、腰椎和股骨BMD明显降低,胫骨和腰椎骨小梁体积、骨小梁宽度、骨小梁数减少,骨小梁间距增加,胫骨骨吸收表面、MAR增大;骨组织TGF-β1、IGF-I、OPN mRNA表达升高,RANKL/OPG比例升高;腰椎压缩和股骨三点弯最大载荷明显降低;血PTH、ALP、尿Pyd / Cr显著升高,血1α,25(OH)2D3显著降低。萌格旺治疗组肾功能和组织结构无显著改善,但血1,25(OH)2D3升高、尿Pyd / Cr降低、骨吸收表面降低、骨量提高、生物力学性能改善。1Gy、5Gy、10Gyγ射线照射后肾小管上皮细胞增
殖能力降低,细胞数减少,1α羟化酶、24羟化酶mRNA 表达降低,TGF-βmRNA表达增高。PTH(1～34)可显著抑制肾小管上皮细胞增殖,促进1α羟化酶基因表达,抑制24羟化酶基因表达,而25(OH)D3对肾小管上皮细胞增殖的影响较小,可促进24羟化酶的表达,而抑制1α羟化酶基因表达。正常肾小管上皮细胞培养上清液可促进成骨细胞增殖、分化和相关基因mRNA表达,降低RANKL/OPG比值,提高碱性磷酸酶活性和矿化结节形成率。受不同剂量射线照射后的肾小管上皮细胞培养上清液对成骨细胞增殖、基因表达和矿化功能的促进作用降低,且剂量越高,作用越弱。抗TGF-β抗体、抗IGF-I抗体和抗OPN抗体均可部分影响肾小管上皮细胞对成骨细胞增殖和功能的调节作用。
结论 (1)15Gy 137Cs-γ射线局部照射大鼠肾脏引起肾组织病理和肾功能进行性损伤;(2)肾辐射损伤诱发明显的骨结构破坏、骨量减少、生物力学性能降低,呈骨转换加速的病理特点;(3)肾辐射骨损伤的主要机制是肾1α羟化酶活性下调致活性维生素D合成障碍,并出现继发性PTH升高,导致骨代谢失平衡;(4)1Gy、5Gy、10Gy γ射线可导致肾小管上皮细胞增殖和功能的降低;(5)肾小管上皮细胞培养上清液对成骨细胞增殖和功能有促进作用,可能是骨重建调节机制之一;(6)TGF-β、IGF-I、OPN参与肾小管上皮细胞对成骨细胞增殖和功能的调节。
Objective Renal injury induced by abdomen radio-therapy, known as radiation nephropathy, is one of the serious complications of this therapy. The pathological characteristics and mechanisms of radiation nephropathy have not been fully understood. Renal osteodystrophy is characterized by various in pathological representations and mechanisms. The present study has established a rat model of renal osteodystrophy by directly irradiation of both kidneys with γ rays. Meanwhile, the primary renal tubule cells and osteoblasts were used to study the pathological characteristics of kidney and bone as well as the possible cellular molecular mechanisms of this disease. By doing so, it is hoped to provide some useful information for preventing and therapy of this disease.
Methods Rat model of irradiation-induced renal injury was established by subjecting both kidneys to 15 Gy Cs137 γ-rays after surgical exposure. 5/6 nephrectomy model was used as compare. Serum and urinal parameters were analyzed by means of RIA, MIA and autoanalyzer. Pathological characteristics of kidneys and bones were studied by light microscope, SEM and TEM. Bone mineral density of lumbar and femurs were determined by DEXA and physical density detector. The dry weight and ash weight of lumbar and femurs were measured. Decalcified slides of lumbar and un-decalcified slides of tibia were made for bone histomorphometry. Biomechanical property of lumbar and femurs were also detected. The mRNA level of TGF-β,OPN,IGF-I,COL-I,VDR,1α-hydroxylase and 24- hydroxylase in the kidney and of TGF-β,OPN,IGF-I,COL-I,VDR,OPG and RANKL in the bone were determined by RT-PCR. The protein level of TGF-β,OPN,IGF-I was determined by Western blot. Primary renal tubule
epithelial cells were subjected to 1Gy,5Gy,10Gy γ rays, as well as to PTH(1～34) and 25(OH)D3.The effects of these factors on proliferation and function of renal tubule epithelial cells were studied. Finally, the effects of culture medium of renal tubule epithelial cells on proliferation and function of primary osteoblasts were studied.
Results Irradiation of both kidneys with 15 Gy Cs137 γ-rays resulted in progressive letdown of renal function, especially of tubule function. The pathological exhibition includes reducing in mass, swell of glomerular, that Bowman’s capsules straitened or disappeared, and some epithelia denaturalized or died. The Mitochondria of tubule epithelial cells were tumefied and the cristae were shortened, lessened and disordered. Progressive fibrosis in renal matrix was found. The mRNA and protein level of TGF-β1 were augmented. The mRNA level of 1α-hydroxylase,24 –hydroxylase and VDR was decreased. The dry weight and ash weight, BMD of femur and lumbar were significantly reduced. TV/BV,Tb.Th,Tb.N of tibia and lumbar were distinctly decreased and Tb.Sp was increased. The mRNA level of TGF-β1,IGF-I,OPN in bone was increased, and the ratio of RANKL/OPG was increased. The maximum load of lumbar and femur were significantly reduced. In the serum, PTH,total ALP were increased and 1,25(OH)2D3 was significantly decreased. The Pyd/Cr in urine was increased. Treating rat with BONE-ONE after irradiation had little effect on renal function and structure, but could result in increasing in bone mass and bone biomechanical property. Irradiation of renal tubule cells with 1Gy,5Gy,10Gyγ-rays resulted in decreasing in proliferation and cell number. The mRNA level of 1α-hydroxylase and 24 –hydroxylase were also reduced, while TGF-βmRNA level was increased. PTH(1～34) significantly suppressed proliferation of tubule epithelial cells, while promoted expression of 1α-hydroxylase and suppressed expression of 24-hydroxylase. 25(OH)D3 had little effect on proliferation of tubule epithelial cells, but promoted expression of 24-hydroxylase and suppressed expression of 1α-hydroxylase. The culture medium of renal tubule epithelial cells significantly promoted proliferation and differentiation of osteoblasts, enhanced expression of related genes (and),
reduced the ratio
引文
Bouillon R, Carmeliet G, Daci E, et al. Vitamin D metabolism and action Osteoporos Int 1998, 8(Suppl 2):S13-19
Kaplan NM, Palmer BF. Update on Renal Ostedystrophy:Pathogenesis and Clinical Management. Am J Med Sci. 1999, 317(4):251-260
Suzuki M. Complications suffered by dialysis patients: Ca and P metabolism disorders of bone. Nippon Naika Gakkai Zasshi 2000,89(7):1358-1365
毛秉智,陈家佩主编.急性放射病基础与临床. 军事医学科学院出版社;2002年,第一版:119-121
Robbins ME, Bonsib SM, Soranson JA, et al. Radiation-induced changes in glomerular and tubular cell kinetics and morphology following irradiation of a single kidney in the pig. International Journal of Radiation Oncology, Biology, Physics 1995,32(4):1071-1081
Salonen J, Saxen L, Lehtonen E, et al.[3H]-adenine metabolism and radiation damage during in vitro development of the kidney. Journal of Histochemistry & Cytochemistry 1992,40(8):1173-1182
Robbins ME, Soranson JA, Wilson GD, et al.Radiation-induced changes in the kinetics of glomerular and tubular cells in the pig kidney. Radiation Research 1994,138(1):107-113
Gobe G, Schoch E, Leighton J.Molecular controls of radiation-induced apoptosis in the neonatal rat kidney. Kidney International,1999, 56(4):1305-1309
Gal-Moscovici A, Rubinger D, Popovtzer MM. 24,25-dihydroxyvitamin D3 in combination with 1,25-dihydroxyvitamin D3 ameliorates renal osteodystrophy in rats with chronic renal failure. Clin Nephrol 2000,53:362-371
Bethea M, Forman DT. Beta 2-microglobulin:its significance and clinical usefulness. Ann Clin Lab Sci 1990, 20(3):163-168
Jaenke RS, Robbins MEC, Bywaters T, et al. Capillary endothelium: target site of renal radiation injury. Laboratory Investigation 1993, 68:396-405
Juncos LI, Cornejo JC, Gomes J, et al. Abnormal endothelium-dependent responses in early radiation nephropathy. Hypertension 1997, 30:672-676
Robbins ME, Bonsib SM. Radiation nephropathy: a review. Scanning Microsc 1995, 9:535-560
Stephens LC, Robbins ME, Johnston DA, et al. Radiation nephropathy in the rhesus monkey: morphometric analysis of glomerular and tubular alterations. Int J Radiat Oncol Biol Phys 1995, 31:865-873
Yildiz F, Atahan IL, Tuncel M, et al. The influence of dose per fraction on the pathogenesis of radiation nephropathy. Australas Radiol 1998, 42:347-353
Robbins ME, Campling D, Rezvani M, et al. Radiation nephropathy in mature pigs following the irradiation of both kidneys. Int J Radiat Biol 1989, 56:83-98
Stewart FA, Te Poele JA, Van der Wal AF, et al. Radiation nephropathy--the link between functional damage and vascular mediated inflammatory and thrombotic changes. Acta Oncol 2001, 40:952-957
Border WA, Noble NA. Interactions of transforming growth factor βand angiotensin II in renal fibrosis. Hypertension 1998, 31:181-188
Cohen EP, Bonsib SA, Whitehouse E, et al. Mediators and mechanisms of radiation nephropathy. Proc Soc Exp Biol Med, 2000, 223:218-225.
Ihn H. Pathogenesis of fibrosis: role of TGF-beta and CTGF. Curr Opin Rheumatol 2002, 14:681-685
Gressner AM, Weiskirchen R, Breitkopf K, et al. Roles of TGF-beta in hepatic fibrosis. Front Biosci 2002, 7:793-807
Goldfarb S, Ziyadeh FN. TGF-beta: a crucial component of the pathogenesis of diabetic nephropathy. Trans Am Clin Climatol Assoc 2001, 112:27-33
Fukuda K, Yoshitomi K, Yanagida T, et al. Quantification of TGF-beta1 mRNA along rat nephron in obstructive nephropathy. Am J Physiol Renal Physiol 2001, 281:513-521
Robbins ME, O'Malley Y, Zhao W, et al. The role of the tubulointerstitium in radiation-induced renal fibrosis. Radiat Res 2001,155(3):481-9
Role of tubular cells in progressive renal disease.van Kooten C, Langers AM, Bruijn JA, Daha MR. Kidney Blood Press Res 1999,22(1-2):53-61
Fan JM, Ng YY, Hill PA, et al. Transforming growth factor-beta regulates tubular epithelial-myofibroblast transdifferentiation in vitro. Kidney Int 1999, 56(4):1455-67
Fan JM, Huang XR, Ng YY, et al.Interleukin-1 induces tubular epithelial-myofibroblast transdifferentiation through a transforming growth factor-beta1-dependent mechanism in vitro. Am J Kidney Dis 2001,37(4):820-31
Ng YY, Huang TP, Yang WC, et al. Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int 1998,54(3):864-76
Zeisberg M, Bonner G, Maeshima Y, et al. Renal fibrosis: collagen composition and assembly regulates epithelial-mesenchymal transdifferentiation. Am J Pathol 2001, 159(4):1313-21
Yamamoto O. Radiation-induced binding of some protein and nucleic acid constituents with macromolecular components in cell systems. Radiat Res 1975,61(2):261-273
Warters RL, Hofer KG,Harris CR, et al. Radionuclide toxicity in cultured mammalian cells: elucidation of the primary site of radiation damage. Curr Top Radiat Res Q 1978,12(1-4):389-407
Goodman, W. G., Coburn, J. W., Slatopolsky, E., and Salusky, I. Renal osteodystrophy in adults and children. In: Favus, M. J., Ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 3rd Edition. Philadelphia, PA: Lippincott-Raven. 1996, 341–360.
Malluche, H. and Faugere, M. C. Renal bone disease 1990: An unmet challenge for the nephrologist. Kidney Int 1990,38:193–211
Bover J, Rodriguez M., Trinidad P, et al. Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat. Kidney Int 1994, 45:953– 961
Fukagawa M, Kaname SY, Igarashi T, et al. Regulation of parathyroid hormone synthesis in chronic renal failure in rats. Kidney Int 1991, 39:874–881
Naveh-Many T, Rahamimov R, Livni N, et al. Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D. J Clin Invest 1995, 96:1786 –1793
Sawaya BP, Koszewski NJ, Qi Q, et al. Secondary hyperparathyroidism and vitamin D receptor binding to vitamin D response elements in rats with incipient renal failure. J Am Soc Nephrol 1997,8:271–278
Omdahl JL, Morris HA, May BK. Hydroxylase enzymes of the vitamin D pathway: expression, function, and regulation. Annual Review of Nutrition 2002, 22:139-66
Zierold C, Mings JA, DeLuca HF. Regulation of 25-hydroxyvitamin D3-24-hydroxylase mRNA by 1,25-dihydroxyvitamin D3 and parathyroid hormone. Journal of Cellular Biochemistry 2003, 88(2):234-7
Patel SR, Ke HQ, Hsu CH. Regulation of calcitriol receptor and its mRNA in normal and renal failure rats. Kidney Int. 45:1020-1027
Farach-Carson MC. Ridall AL. Dual 1,25-dihydroxyvitamin D3 signal response pathways in osteoblasts: cross-talk between genomic and membrane-initiated pathways. American Journal of Kidney Diseases 1998, 31(4):729-42
Thomas G, Moffatt P, Salois P, et al. Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype. J Biol Chem, 2003, 278(50):50563-71
Thomas GP, Baker SU, Eisman JA, et al. Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts. J Endocrinol 2001, 170(2):451-60
Suda T, Ueno Y, Fujii K, et al. Vitamin D and bone. J Cell Biochem 2003, 88(2):259-66
Kitazawa S, Kajimoto K, Kondo T, et al. Vitamin D3 supports osteoclastogenesis via functional vitamin D response element of human RANKL gene promoter. J Cell Biochem 2003, 89(4):771-7
Gurlek A, Kumar R. Regulation of osteoblast growth by interactions between transforming growth factor-beta and 1alpha,25-dihydroxyvitamin D3. Crit Rev Eukaryot Gene Expr 2001,11(4):299-317
Eichner A, Brock J, Heldin CH, et al. Bone morphogenetic protein-7 (OP1) and transforming growth factor-beta1 modulate 1,25(OH)2-vitamin D3-induced differentiation of human osteoblasts. Exp Cell Res 2002, 275(1):132-42
Nagel D, Kumar R. 1 alpha,25-dihydroxyvitamin D3 increases TGF beta 1 binding to human osteoblasts. Biochem Biophys Res Commun 2002, 290(5):1558-63
Finkelman RD, Linkhart TA, Mohan S, et al. Vitamin D deficiency causes a selective reduction in deposition of transforming growth factor beta in rat bone: possible mechanism for impaired osteoinduction. Proc Natl Acad Sci USA 1991, 88(9):3657-3660
Borton AJ, Frederick JP, Datto MB, et al. The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis. J Bone Miner Res 2001,16(10):1754-64
Miller M A., Chin J., Miller SC., et al. Disparate Effects of Mild, Moderate, and Severe Secondary Hyperparathyroidism on Cancellous and Cortical Bone in Rats With Chronic Renal Insufficiency. Bone 1998,23(3):257–266
Bellido T, Ali AA, Plotkin LI, et al. Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem 2003, 278(50):50259-72
Lotinun S, Sibonga JD, Turner RT. Differential effects of intermittent and continuous administration of parathyroid hormone on bone histomorphometry and gene expression. Endocrine 2002, 17(1):29-36
Locklin RM, Khosla S, Turner RT, et al. Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone. Journal of Cellular Biochemistry 2003,89(1):180-90
Ronco P,Antoine M, Baudouin B,et al. Polarized membrane expression of brush-border hydrolases in primary cultures of kidney proximal tubular cells depends on cell differentiation, and is induced by dexamethasone. J Cell Physiol1990,145:222
Evans PJ. Selective inhibition of the synthesis of phosphoenolpyruvate carboxykinase in freshly isolated proximal tubule cells. Biochim Biophys ACTA 1992,1133:255
Aleo MD,Schenellmann RG. Regulation of glycolytic metabilism during long-term primary culture of renal proximal tubule cells. Am J Physiol 1992, 263: F152
Jung JC, Lee SM, Kadakia N, et al. Growth and funtion of primery rabbit kidney proximal tubule cells in glucose-free serum-free medium. J Cell Physiol 1992,150:243
Ming-Jer Tang, Ya-Ren Cheng, and Hsi-Hui Lin Role of Apoptosis in Growth and Differentiation of Proximal Tubule Cells in Primary Cultures. Bioch & Biop Res Commu 1996,218:658–664
Raff MC. Nature 1992,356:397–400
Ishizaki, Y., Voyvodic, J. T., Burne, J. F., and Raff, M. C. (1993) J. Cell Biol. 121, 899–908.
Ishizaki Y, Burne JF, Raff MC. J Cell Biol 1994,126:1069–1077
Robbins ME, Zhao W, Davis CS, et al. Radiation-induced kidney injury: a role for chronic oxidative stress? Micron 2002,33(2):133-41
Miyajima A, Chen J, Kirman I, et al. Interaction of nitric oxide and transforming growth factor-beta1 induced by angiotensin II and mechanical stretch in rat renal tubular epithelial cells. J Urol 2000,164(5):1729-34
Haugen EN, Croatt AJ, Nath KA. Angiotensin II induces renal oxidant stress in vivo and heme oxygenase-1 in vivo and in vitro. Kidney Int 2000, 58(1):144-52
Bhaskaran M, Reddy K, Radhakrishanan N, et al. Angiotensin II induces apoptosis in renal proximal tubular cells. Am J Physiol Renal Physiol 2003,284(5):F955-65
Ueda N, Camargo SM, Hong X, et al. Role of ceramide synthase in oxidant injury to renal tubular epithelial cells. J Am Soc Nephrol 2001,12(11):2384-91
Cecilia M. GiachelliU, Susan Steitz. Osteopontin: a versatile regulator of inflammation and Biomineralization. Matrix Biology 2000,19:615-622
Ophascharoensuk V, Giachelli CM, Gordon K, et al. Obstructive uropathy in the mouse: role of osteopontin in interstitial fibrosis and apoptosis. Kidney Int 1999,56(2):571-80
Noiri E, Dickman K, Miller F, et al. Reduced tolerance to acute renal ischemia in mice with a targeted disruption of the osteopontin gene. Kidney Int 1999,56(1):74-82
Okada H, Moriwaki K, Kalluri R, et al.Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats. Am J Physiol Renal Physiol 2000,278(1):F110-21
Malyankar UM, Almeida M, Johnson RJ, et al. Osteopontin regulation in cultured rat renal epithelial cells. Kidney Int 1997 ,51(6):1766-73
Seki G, Taniguchi S, Uwatoko S,et al. Effect of parathyroid hormone on acid/base transport in rabbit renal proximal tubule S3 segment. Pflugers Archiv - European Journal of Physiology 1993, 423(1-2):7-13
Ribeiro CP, Mandel LJ. Parathyroid hormone inhibits proximal tubule Na(+)-K(+)-ATPase activity. American Journal of Physiology 1992,262(2 Pt 2):F209-16
Laverty G, McWilliams C,Sheldon A,et al. PTH stimulates a Cl(-)-dependent and EIPA-sensitive current in chick proximal tubule cells in culture. American Journal of Physiology - Renal Fluid & Electrolyte Physiology 2003,284(5):F987-95
Siegfried G, Vrtovsnik F, Prie D, et al. Parathyroid hormone stimulates ecto-5'-nucleotidase activity in renal epithelial cells: role of protein kinase-C. Endocrinology 1995,136(3):1267-75
Dudas PL, Villalobos AR, Gocek-Sutterlin G,et al. Regulation of transepithelial phosphate transport by PTH in chicken proximal tubule epithelium. American Journal of Physiology - Regulatory Integrative & Comparative Physiology 2002,282(1):R139-46
Riccardi D, Traebert M, Ward DT,et al. Dietary phosphate and parathyroid hormone alter the expression of the calcium-sensing receptor (CaR) and the Na+-dependent Pi transporter (NaPi-2) in the rat proximal tubule. Pflugers Archiv - European Journal of Physiology 2000,441(2-3):379-87
Traebert M, Roth J, Biber J, et al. Internalization of proximal tubular type II Na-P(i) cotransporter by PTH: immunogold electron microscopy. American Journal of Physiology - Renal Fluid & Electrolyte Physiology 2000, 278(1):F148-54
Lotscher M, Scarpetta Y, Levi M, et al. Rapid downregulation of rat renal Na/P(i) cotransporter in response to parathyroid hormone involves microtubule rearrangement. Journal of Clinical Investigation 1999,104(4):483-94
Zierold C. Mings JA. DeLuca HF. Regulation of 25-hydroxyvitamin D3-24-hydroxylase mRNA by 1,25-dihydroxyvitamin D3 and parathyroid hormone. Journal of Cellular Biochemistry 2003,88(2):234-7
Li-Ping Cao, Merry J. G. Bolt, Minjie Wei, et al. Regulation of calbindin-D9k expression by 1,25-dihydroxyvitamin D3 and parathyroid hormone in mouse primary renal tubular cells. Archives of Biochemistry and Biophysics 2002, 400(1):118–124
王洪复,关本博,林光义. 由胎鼠头盖骨培养成骨细胞的实验技术和细胞形态观察. 上海医科大学学报 1991,18(6):475-477
Thomas AL,Subburarnan M,David JB. Growth factors for bone growth and repair:IGF, TGF and BMP. Bone 1996, 19(1):1s-12s
Kassem M, Kveiborg M, Eriksen EF. Production and action of transforming growth factor-beta in human osteoblast cultures: dependence on cell differentiation and modulation by calcitriol. European Journal of Clinical Investigation 2000, 30(5):429-37
Alliston T, Choy L, Ducy P. TGF-beta-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation. EMBO Journal 2001, 20(9):2254-72
Karsdal MA, Fjording MS, Foged NT, et al. Transforming growth factor-beta-induced osteoblast elongation regulates osteoclastic bone resorption through a p38 mitogen-activated protein kinase- and matrix metalloproteinase-dependent pathway. Journal of Biological Chemistry 2001,276(42):39350-8
Franchimont N, Rydziel S, Canalis E. Transforming growth factor-beta increases interleukin-6 transcripts in osteoblasts. Bone 2000,26(3):249-53
Wagner MS, Stracke S, Jehle PM,et al. Evaluation of IGF system component levels and mitogenic activity of uremic serum on normal human osteoblasts. Nephron 2000,84(2):158-66
Zhang W, Lee JC, Kumar S,et al. ERK pathway mediates the activation of Cdk2 in IGF-1-induced proliferation of human osteosarcoma MG-63 cells. Journal of Bone & Mineral Research 1999,14(4):528-35
Santhanagopal A, Dixon SJ. Insulin-like growth factor I rapidly enhances acid efflux from osteoblastic cells. American Journal of Physiology 1999,277(3 Pt 1):E423-32
Liu YK, Uemura T,Nemoto A,et al. Osteopontin involvement in integrin-mediated cell signaling and regulation of expression of alkaline phosphatase during early differentiation of UMR cells. FEBS 1997, 420:112-116
Uemura T, Nemoto A, Liu YK, et al. Osteopontin involvement in bone remodeling and its effects on in vivo osteogenic potential of bone marrow-derived osteoblastsrporous hydroxyapatite constructs. Materials Science and Engineering C 2001, 17:33–36
Cecilia M. GiachelliU, Susan Steitz. Osteopontin: a versatile regulator of inflammation and Biomineralization. Matrix Biology 2000,19:615-622
参考书目
夏寿萱主编.放射生物学.北京,军事医学科学院出版社;1998年,第一版。
刘忠厚主编.骨质疏松学. 北京,科学出版社;1998年,第一版。
钟慈声主编.细胞和组织的超微结构.北京,人民卫生出版社;1984年,第一版。
黄培堂 等译 分子克隆实验指南. 科学出版社;2002年,第三版。
黄培堂 等译.PCR技术实验指南. 科学出版社;1998年,第一版。
金惠铭主编.病理生理学. 北京,人民卫生出版社;1997年,第四版。
汪仁主编.细胞生物学. 北京,北京师范大学出版社;1990年,第一版。
姚泰主编.人体生理学. 北京,人民卫生出版社;2001年,第三版。
成令忠,钟翠平,蔡文琴主编.现代组织学.上海,上海科学技术文献出版社;2003年,第一版.
陈瑗,周玫主编.自由基医学基础与病理生理. 北京,人民卫生出版社;2002年,第一版。
Barry M. Brenner. The Kidney.Six Edition. 北京,科学出版社;2001年,第一版。
Kaplan NM, Palmer BF. Update on Renal Ostedystrophy:Pathogenesis and Clinical Management. Am J Med Sci. 1999, 317(4):251-260
Suzuki M. Complications suffered by dialysis patients: Ca and P metabolism disorders of bone. Nippon Naika Gakkai Zasshi 2000,89(7):1358-1365
毛秉智,陈家佩主编.急性放射病基础与临床. 军事医学科学院出版社;2002年,第一版:119-121
Robbins ME, Bonsib SM, Soranson JA, et al. Radiation-induced changes in glomerular and tubular cell kinetics and morphology following irradiation of a single kidney in the pig. International Journal of Radiation Oncology, Biology, Physics 1995,32(4):1071-1081
Salonen J, Saxen L, Lehtonen E, et al.[3H]-adenine metabolism and radiation damage during in vitro development of the kidney. Journal of Histochemistry & Cytochemistry 1992,40(8):1173-1182
Robbins ME, Soranson JA, Wilson GD, et al.Radiation-induced changes in the kinetics of glomerular and tubular cells in the pig kidney. Radiation Research 1994,138(1):107-113
Gobe G, Schoch E, Leighton J.Molecular controls of radiation-induced apoptosis in the neonatal rat kidney. Kidney International,1999, 56(4):1305-1309
Gal-Moscovici A, Rubinger D, Popovtzer MM. 24,25-dihydroxyvitamin D3 in combination with 1,25-dihydroxyvitamin D3 ameliorates renal osteodystrophy in rats with chronic renal failure. Clin Nephrol 2000,53:362-371
Bethea M, Forman DT. Beta 2-microglobulin:its significance and clinical usefulness. Ann Clin Lab Sci 1990, 20(3):163-168
Jaenke RS, Robbins MEC, Bywaters T, et al. Capillary endothelium: target site of renal radiation injury. Laboratory Investigation 1993, 68:396-405
Juncos LI, Cornejo JC, Gomes J, et al. Abnormal endothelium-dependent responses in early radiation nephropathy. Hypertension 1997, 30:672-676
Robbins ME, Bonsib SM. Radiation nephropathy: a review. Scanning Microsc 1995, 9:535-560
Stephens LC, Robbins ME, Johnston DA, et al. Radiation nephropathy in the rhesus monkey: morphometric analysis of glomerular and tubular alterations. Int J Radiat Oncol Biol Phys 1995, 31:865-873
Yildiz F, Atahan IL, Tuncel M, et al. The influence of dose per fraction on the pathogenesis of radiation nephropathy. Australas Radiol 1998, 42:347-353
Robbins ME, Campling D, Rezvani M, et al. Radiation nephropathy in mature pigs following the irradiation of both kidneys. Int J Radiat Biol 1989, 56:83-98
Stewart FA, Te Poele JA, Van der Wal AF, et al. Radiation nephropathy--the link between functional damage and vascular mediated inflammatory and thrombotic changes. Acta Oncol 2001, 40:952-957
Border WA, Noble NA. Interactions of transforming growth factor βand angiotensin II in renal fibrosis. Hypertension 1998, 31:181-188
Cohen EP, Bonsib SA, Whitehouse E, et al. Mediators and mechanisms of radiation nephropathy. Proc Soc Exp Biol Med, 2000, 223:218-225.
Ihn H. Pathogenesis of fibrosis: role of TGF-beta and CTGF. Curr Opin Rheumatol 2002, 14:681-685
Gressner AM, Weiskirchen R, Breitkopf K, et al. Roles of TGF-beta in hepatic fibrosis. Front Biosci 2002, 7:793-807
Goldfarb S, Ziyadeh FN. TGF-beta: a crucial component of the pathogenesis of diabetic nephropathy. Trans Am Clin Climatol Assoc 2001, 112:27-33
Fukuda K, Yoshitomi K, Yanagida T, et al. Quantification of TGF-beta1 mRNA along rat nephron in obstructive nephropathy. Am J Physiol Renal Physiol 2001, 281:513-521
Robbins ME, O'Malley Y, Zhao W, et al. The role of the tubulointerstitium in radiation-induced renal fibrosis. Radiat Res 2001,155(3):481-9
Role of tubular cells in progressive renal disease.van Kooten C, Langers AM, Bruijn JA, Daha MR. Kidney Blood Press Res 1999,22(1-2):53-61
Fan JM, Ng YY, Hill PA, et al. Transforming growth factor-beta regulates tubular epithelial-myofibroblast transdifferentiation in vitro. Kidney Int 1999, 56(4):1455-67
Fan JM, Huang XR, Ng YY, et al.Interleukin-1 induces tubular epithelial-myofibroblast transdifferentiation through a transforming growth factor-beta1-dependent mechanism in vitro. Am J Kidney Dis 2001,37(4):820-31
Ng YY, Huang TP, Yang WC, et al. Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int 1998,54(3):864-76
Zeisberg M, Bonner G, Maeshima Y, et al. Renal fibrosis: collagen composition and assembly regulates epithelial-mesenchymal transdifferentiation. Am J Pathol 2001, 159(4):1313-21
Yamamoto O. Radiation-induced binding of some protein and nucleic acid constituents with macromolecular components in cell systems. Radiat Res 1975,61(2):261-273
Warters RL, Hofer KG,Harris CR, et al. Radionuclide toxicity in cultured mammalian cells: elucidation of the primary site of radiation damage. Curr Top Radiat Res Q 1978,12(1-4):389-407
Goodman, W. G., Coburn, J. W., Slatopolsky, E., and Salusky, I. Renal osteodystrophy in adults and children. In: Favus, M. J., Ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 3rd Edition. Philadelphia, PA: Lippincott-Raven. 1996, 341–360.
Malluche, H. and Faugere, M. C. Renal bone disease 1990: An unmet challenge for the nephrologist. Kidney Int 1990,38:193–211
Bover J, Rodriguez M., Trinidad P, et al. Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat. Kidney Int 1994, 45:953– 961
Fukagawa M, Kaname SY, Igarashi T, et al. Regulation of parathyroid hormone synthesis in chronic renal failure in rats. Kidney Int 1991, 39:874–881
Naveh-Many T, Rahamimov R, Livni N, et al. Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D. J Clin Invest 1995, 96:1786 –1793
Sawaya BP, Koszewski NJ, Qi Q, et al. Secondary hyperparathyroidism and vitamin D receptor binding to vitamin D response elements in rats with incipient renal failure. J Am Soc Nephrol 1997,8:271–278
Omdahl JL, Morris HA, May BK. Hydroxylase enzymes of the vitamin D pathway: expression, function, and regulation. Annual Review of Nutrition 2002, 22:139-66
Zierold C, Mings JA, DeLuca HF. Regulation of 25-hydroxyvitamin D3-24-hydroxylase mRNA by 1,25-dihydroxyvitamin D3 and parathyroid hormone. Journal of Cellular Biochemistry 2003, 88(2):234-7
Patel SR, Ke HQ, Hsu CH. Regulation of calcitriol receptor and its mRNA in normal and renal failure rats. Kidney Int. 45:1020-1027
Farach-Carson MC. Ridall AL. Dual 1,25-dihydroxyvitamin D3 signal response pathways in osteoblasts: cross-talk between genomic and membrane-initiated pathways. American Journal of Kidney Diseases 1998, 31(4):729-42
Thomas G, Moffatt P, Salois P, et al. Osteocrin, a novel bone-specific secreted protein that modulates the osteoblast phenotype. J Biol Chem, 2003, 278(50):50563-71
Thomas GP, Baker SU, Eisman JA, et al. Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts. J Endocrinol 2001, 170(2):451-60
Suda T, Ueno Y, Fujii K, et al. Vitamin D and bone. J Cell Biochem 2003, 88(2):259-66
Kitazawa S, Kajimoto K, Kondo T, et al. Vitamin D3 supports osteoclastogenesis via functional vitamin D response element of human RANKL gene promoter. J Cell Biochem 2003, 89(4):771-7
Gurlek A, Kumar R. Regulation of osteoblast growth by interactions between transforming growth factor-beta and 1alpha,25-dihydroxyvitamin D3. Crit Rev Eukaryot Gene Expr 2001,11(4):299-317
Eichner A, Brock J, Heldin CH, et al. Bone morphogenetic protein-7 (OP1) and transforming growth factor-beta1 modulate 1,25(OH)2-vitamin D3-induced differentiation of human osteoblasts. Exp Cell Res 2002, 275(1):132-42
Nagel D, Kumar R. 1 alpha,25-dihydroxyvitamin D3 increases TGF beta 1 binding to human osteoblasts. Biochem Biophys Res Commun 2002, 290(5):1558-63
Finkelman RD, Linkhart TA, Mohan S, et al. Vitamin D deficiency causes a selective reduction in deposition of transforming growth factor beta in rat bone: possible mechanism for impaired osteoinduction. Proc Natl Acad Sci USA 1991, 88(9):3657-3660
Borton AJ, Frederick JP, Datto MB, et al. The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis. J Bone Miner Res 2001,16(10):1754-64
Miller M A., Chin J., Miller SC., et al. Disparate Effects of Mild, Moderate, and Severe Secondary Hyperparathyroidism on Cancellous and Cortical Bone in Rats With Chronic Renal Insufficiency. Bone 1998,23(3):257–266
Bellido T, Ali AA, Plotkin LI, et al. Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism. J Biol Chem 2003, 278(50):50259-72
Lotinun S, Sibonga JD, Turner RT. Differential effects of intermittent and continuous administration of parathyroid hormone on bone histomorphometry and gene expression. Endocrine 2002, 17(1):29-36
Locklin RM, Khosla S, Turner RT, et al. Mediators of the biphasic responses of bone to intermittent and continuously administered parathyroid hormone. Journal of Cellular Biochemistry 2003,89(1):180-90
Ronco P,Antoine M, Baudouin B,et al. Polarized membrane expression of brush-border hydrolases in primary cultures of kidney proximal tubular cells depends on cell differentiation, and is induced by dexamethasone. J Cell Physiol1990,145:222
Evans PJ. Selective inhibition of the synthesis of phosphoenolpyruvate carboxykinase in freshly isolated proximal tubule cells. Biochim Biophys ACTA 1992,1133:255
Aleo MD,Schenellmann RG. Regulation of glycolytic metabilism during long-term primary culture of renal proximal tubule cells. Am J Physiol 1992, 263: F152
Jung JC, Lee SM, Kadakia N, et al. Growth and funtion of primery rabbit kidney proximal tubule cells in glucose-free serum-free medium. J Cell Physiol 1992,150:243
Ming-Jer Tang, Ya-Ren Cheng, and Hsi-Hui Lin Role of Apoptosis in Growth and Differentiation of Proximal Tubule Cells in Primary Cultures. Bioch & Biop Res Commu 1996,218:658–664
Raff MC. Nature 1992,356:397–400
Ishizaki, Y., Voyvodic, J. T., Burne, J. F., and Raff, M. C. (1993) J. Cell Biol. 121, 899–908.
Ishizaki Y, Burne JF, Raff MC. J Cell Biol 1994,126:1069–1077
Robbins ME, Zhao W, Davis CS, et al. Radiation-induced kidney injury: a role for chronic oxidative stress? Micron 2002,33(2):133-41
Miyajima A, Chen J, Kirman I, et al. Interaction of nitric oxide and transforming growth factor-beta1 induced by angiotensin II and mechanical stretch in rat renal tubular epithelial cells. J Urol 2000,164(5):1729-34
Haugen EN, Croatt AJ, Nath KA. Angiotensin II induces renal oxidant stress in vivo and heme oxygenase-1 in vivo and in vitro. Kidney Int 2000, 58(1):144-52
Bhaskaran M, Reddy K, Radhakrishanan N, et al. Angiotensin II induces apoptosis in renal proximal tubular cells. Am J Physiol Renal Physiol 2003,284(5):F955-65
Ueda N, Camargo SM, Hong X, et al. Role of ceramide synthase in oxidant injury to renal tubular epithelial cells. J Am Soc Nephrol 2001,12(11):2384-91
Cecilia M. GiachelliU, Susan Steitz. Osteopontin: a versatile regulator of inflammation and Biomineralization. Matrix Biology 2000,19:615-622
Ophascharoensuk V, Giachelli CM, Gordon K, et al. Obstructive uropathy in the mouse: role of osteopontin in interstitial fibrosis and apoptosis. Kidney Int 1999,56(2):571-80
Noiri E, Dickman K, Miller F, et al. Reduced tolerance to acute renal ischemia in mice with a targeted disruption of the osteopontin gene. Kidney Int 1999,56(1):74-82
Okada H, Moriwaki K, Kalluri R, et al.Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats. Am J Physiol Renal Physiol 2000,278(1):F110-21
Malyankar UM, Almeida M, Johnson RJ, et al. Osteopontin regulation in cultured rat renal epithelial cells. Kidney Int 1997 ,51(6):1766-73
Seki G, Taniguchi S, Uwatoko S,et al. Effect of parathyroid hormone on acid/base transport in rabbit renal proximal tubule S3 segment. Pflugers Archiv - European Journal of Physiology 1993, 423(1-2):7-13
Ribeiro CP, Mandel LJ. Parathyroid hormone inhibits proximal tubule Na(+)-K(+)-ATPase activity. American Journal of Physiology 1992,262(2 Pt 2):F209-16
Laverty G, McWilliams C,Sheldon A,et al. PTH stimulates a Cl(-)-dependent and EIPA-sensitive current in chick proximal tubule cells in culture. American Journal of Physiology - Renal Fluid & Electrolyte Physiology 2003,284(5):F987-95
Siegfried G, Vrtovsnik F, Prie D, et al. Parathyroid hormone stimulates ecto-5'-nucleotidase activity in renal epithelial cells: role of protein kinase-C. Endocrinology 1995,136(3):1267-75
Dudas PL, Villalobos AR, Gocek-Sutterlin G,et al. Regulation of transepithelial phosphate transport by PTH in chicken proximal tubule epithelium. American Journal of Physiology - Regulatory Integrative & Comparative Physiology 2002,282(1):R139-46
Riccardi D, Traebert M, Ward DT,et al. Dietary phosphate and parathyroid hormone alter the expression of the calcium-sensing receptor (CaR) and the Na+-dependent Pi transporter (NaPi-2) in the rat proximal tubule. Pflugers Archiv - European Journal of Physiology 2000,441(2-3):379-87
Traebert M, Roth J, Biber J, et al. Internalization of proximal tubular type II Na-P(i) cotransporter by PTH: immunogold electron microscopy. American Journal of Physiology - Renal Fluid & Electrolyte Physiology 2000, 278(1):F148-54
Lotscher M, Scarpetta Y, Levi M, et al. Rapid downregulation of rat renal Na/P(i) cotransporter in response to parathyroid hormone involves microtubule rearrangement. Journal of Clinical Investigation 1999,104(4):483-94
Zierold C. Mings JA. DeLuca HF. Regulation of 25-hydroxyvitamin D3-24-hydroxylase mRNA by 1,25-dihydroxyvitamin D3 and parathyroid hormone. Journal of Cellular Biochemistry 2003,88(2):234-7
Li-Ping Cao, Merry J. G. Bolt, Minjie Wei, et al. Regulation of calbindin-D9k expression by 1,25-dihydroxyvitamin D3 and parathyroid hormone in mouse primary renal tubular cells. Archives of Biochemistry and Biophysics 2002, 400(1):118–124
王洪复,关本博,林光义. 由胎鼠头盖骨培养成骨细胞的实验技术和细胞形态观察. 上海医科大学学报 1991,18(6):475-477
Thomas AL,Subburarnan M,David JB. Growth factors for bone growth and repair:IGF, TGF and BMP. Bone 1996, 19(1):1s-12s
Kassem M, Kveiborg M, Eriksen EF. Production and action of transforming growth factor-beta in human osteoblast cultures: dependence on cell differentiation and modulation by calcitriol. European Journal of Clinical Investigation 2000, 30(5):429-37
Alliston T, Choy L, Ducy P. TGF-beta-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation. EMBO Journal 2001, 20(9):2254-72
Karsdal MA, Fjording MS, Foged NT, et al. Transforming growth factor-beta-induced osteoblast elongation regulates osteoclastic bone resorption through a p38 mitogen-activated protein kinase- and matrix metalloproteinase-dependent pathway. Journal of Biological Chemistry 2001,276(42):39350-8
Franchimont N, Rydziel S, Canalis E. Transforming growth factor-beta increases interleukin-6 transcripts in osteoblasts. Bone 2000,26(3):249-53
Wagner MS, Stracke S, Jehle PM,et al. Evaluation of IGF system component levels and mitogenic activity of uremic serum on normal human osteoblasts. Nephron 2000,84(2):158-66
Zhang W, Lee JC, Kumar S,et al. ERK pathway mediates the activation of Cdk2 in IGF-1-induced proliferation of human osteosarcoma MG-63 cells. Journal of Bone & Mineral Research 1999,14(4):528-35
Santhanagopal A, Dixon SJ. Insulin-like growth factor I rapidly enhances acid efflux from osteoblastic cells. American Journal of Physiology 1999,277(3 Pt 1):E423-32
Liu YK, Uemura T,Nemoto A,et al. Osteopontin involvement in integrin-mediated cell signaling and regulation of expression of alkaline phosphatase during early differentiation of UMR cells. FEBS 1997, 420:112-116
Uemura T, Nemoto A, Liu YK, et al. Osteopontin involvement in bone remodeling and its effects on in vivo osteogenic potential of bone marrow-derived osteoblastsrporous hydroxyapatite constructs. Materials Science and Engineering C 2001, 17:33–36
Cecilia M. GiachelliU, Susan Steitz. Osteopontin: a versatile regulator of inflammation and Biomineralization. Matrix Biology 2000,19:615-622
参考书目
夏寿萱主编.放射生物学.北京,军事医学科学院出版社;1998年,第一版。
刘忠厚主编.骨质疏松学. 北京,科学出版社;1998年,第一版。
钟慈声主编.细胞和组织的超微结构.北京,人民卫生出版社;1984年,第一版。
黄培堂 等译 分子克隆实验指南. 科学出版社;2002年,第三版。
黄培堂 等译.PCR技术实验指南. 科学出版社;1998年,第一版。
金惠铭主编.病理生理学. 北京,人民卫生出版社;1997年,第四版。
汪仁主编.细胞生物学. 北京,北京师范大学出版社;1990年,第一版。
姚泰主编.人体生理学. 北京,人民卫生出版社;2001年,第三版。
成令忠,钟翠平,蔡文琴主编.现代组织学.上海,上海科学技术文献出版社;2003年,第一版.
陈瑗,周玫主编.自由基医学基础与病理生理. 北京,人民卫生出版社;2002年,第一版。
Barry M. Brenner. The Kidney.Six Edition. 北京,科学出版社;2001年,第一版。