RESEARCH PROGRESS OF BONE MORPHOGENETIC PROTEIN AND LIABILITY OF OSSIFICATION OF POSTERIOR LONGITUDINAL LIGAMENT_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

FANG Zhao ¹ , SUN Tianwei ² , Sandip Kumar Yadav ²

1Department of Spinal Surgery, Nankai University Affiliated Hospital, Tianjin, 300121, P.R.China;;
2Department of Spinal Surgery, Tianjin Union Medicine Centre, School of Clinical Medicine, Tianjin Medical University. Corresponding author: SUN Tianwei, E-mail: billsuntw@163.com;

Corresponding author：

Keywords：

Ossification of the posterior longitudinal ligament; Bone morphogenetic protein; Single nucleotide polymorphisms; Susceptibility; Liability

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Objective To review the research progress of bone morphogenetic protein (BMP) and the liability of ossification of the posterior longitudinal ligament (OPLL). Methods Recent literature concerning BMP and the liability of OPLL was reviewed, analysed, and summarized. Results The single nucleotide polymorphisms (SNPs) of BMP gene may produce a minor cumulative effect and increase individual susceptibility to OPLL. A variety of environmental factors can promote the occurrence and development of OPLL by increasing the expression of BMP gene. Conclusion The SNPs of BMP gene may increase individual susceptibility to OPLL. However, interaction of cumulative effect of the SNPs and environmental factors can promote the liability to OPLL.

Citation： FANG Zhao,SUN Tianwei,Sandip Kumar Yadav. RESEARCH PROGRESS OF BONE MORPHOGENETIC PROTEIN AND LIABILITY OF OSSIFICATION OF POSTERIOR LONGITUDINAL LIGAMENT. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(10): 1255-1258. doi: Copy

1.	Barnes GL, Kostenuik PJ, Gerstenfeld LC, et al. Growth factor regulation of fracture repair. J Bone Miner Res, 1999, 14(11): 1805-1815.
2.	Tanaka H, Nagai E, Murata H, et al. Involvement of bone morphogenic protein-2 in the pathological ossification process of the spinal ligament. Rheumatology (Oxford), 2001, 40(10): 1163-1168.
3.	陈棣, 叶伟胜. 骨形态发生蛋白的成骨功能及临床应用. 中华外科杂志, 1996, 34(10): 602-605.
4.	Sampath T, Maliakal J, Hauschka P, et al. Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differention in vitro. J Biol Chem, 1992, 267(28): 20352-20362.
5.	Inamasu J, Guiot BH, Sachs DC. Ossification of the posterior longitudinal ligament: an update on its biology, epidemiology, and natural history. Neurosurgery, 2006, 58(6): 1027-1039.
6.	Wang H, Liu D, Yang Z, et al. Association of bone morphogenetic protein-2 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the spine and its severity in Chinese patients. Eur Spine J, 2008, 1(7): 956-964.
7.	Wang H, Yang ZH, Liu DM, et al. Association between two polymorphisms of the bone morpho-genetic protein-2 gene with genetic susceptibility to ossification of the posterior longitudinal ligament of the cervical spine and its severity. Chin Med J (Engl), 2008, 121(18): 1806-1810.
8.	Furushima K, Shimo-Onoda A, Maeda S, et al. Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine. J Bone Miner Res, 2002, 17(1): 128-137.
9.	Meng XL, Wang H, Yang H, et al. T allele at site 6007 of bone morphogenetic protein-4 gene increases genetic susceptibility to ossification of the posterior longitudinal ligament in male Chinese Han population. Chin Med J (Engl), 2010, 123(18): 2537-2542.
10.	赵伟光, 谢延平, 闫亮, 等. 骨形态发生蛋白-4基因单核苷酸多态性与颈椎后纵韧带骨化症. 中国康复理论与实践, 2011, 17(1): 39-41.
11.	Ren Y, Feng J, Liu ZZ, et al. A new haplotypein BMP4 implicated in ossification of the posterior longitudinal ligament (OPLL) in a Chinese population. J Orthop Res, 2012, 30(5): 748-756.
12.	Yonemori K, Imamura T, Ishidou Y, et al. Bone morphogenetic protein receptors and activin receptors are highly expressed in ossified ligament tissues of patients with ossification of the posterior longitudinal ligament. Am J Pathol, 1997, 150(4): 1335-1347.
13.	Freedman BI, Bowden DW, Ziegler JT, et al. Bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with inverse relationships between vascular calcification and BMD: the diabetes heart study. J Bone Miner Res, 2009, 24(10): 1719-1727.
14.	Yan L, Zhao WG, Li JJ, et al. Linkage of three polymorphisms on chromosome 20p12 to ossification of the posterior longitudinal ligament of spine and its severity in Han Chinese patients. Chin Med J (Engl), 2010, 123(17): 2341-2346.
15.	Chen D, Harris MA, Rossin G, et al. Bone morphogenetic protein 2 (BMP-2) enhances BMP-3, BMP-4, and bone cell differentiation marker gene expression during the induction of mineralized bone matrix formation in cultures of fetal rat calvarial osteoblasts. Calcif Tissue Int, 1997, 60(3): 283-290.
16.	Miyazono K, Maeda S, Imamura T. BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev, 2005, 16(3): 251-263.
17.	Tsai AD, Yeh LC, Lee JC. Effects of osteogenic protein-1 (OP-1, BMP-7) on gene expression in cultured medial collateral ligament cells. J Cell Biochem, 2003, 90(4): 777-791.
18.	Stetler WR, La Marca F, Park P. The genetics of ossification of the posterior longitudinal ligament. Neurosurg Focus, 2011, 30(3): E7.
19.	Li H, Jiang LS, Dai LY. High glucose potentiates collagen synthesis and bone morphogenetic protein-2-induced early osteoblast gene expression in rat spinal ligament cells. Endocrinology, 2010, 151(1): 63-74.
20.	Baba H, Furusawa N, Fukuda M, et al. Potential role of streptozotocin in enhancing ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy). Eur J Histochem, 1997, 41(3): 191-202.
21.	Yokosuka K, Park JS, Jimbo K, et al. Immunohistochemical demonstration of advanced glycation end products and the effects of advanced glycation end products in ossified ligament tissues in vitro. Spine (Phila Pa 1976), 2007, 32(11): E337-339.
22.	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 phosphat idylinositol 3-kinase. Spine (Phila Pa 1976), 2011, 33(22): 2394-2402.
23.	Ikeda Y, Nakajima A, Aiba A, et al. Association between serum leptin and bone metabolic markers, and the development of heterotopic ossification of the spinal ligament in female patients with ossification of the posterior longitudinal ligament. Eur Spine J, 2011, 20(9): 1450-1458.
24.	Tanno M, Furukawa KI, Ueyama K, et al. Unixial cyclic stretch induces osteogenic differention and synthesis of bone morphogenetic proteins of spine ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003, 33(4): 475-484.
25.	Tsukamoto N, Maeda T, Miura H, et al. Repetitive tensile stress to rat caudal vertrbrae induing cartilage formation in the spinal ligaments: a possible role of mechanial stress in the development of ossification of the spinal ligaments. J Neurosurg Spine, 2006, 5(3): 234-242.
26.	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.
27.	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.
28.	Ghosh-Choudhury N, Harris MA, Feng JQ, et al. Expression of the BMP2 gene during bone cell differentiation. Crit Rev Eukaryot Gene Expr, 1994, 4(2-3): 345-355.
29.	Tanaka S, Kudo H, Asari T, et al. P2Y1 transient overexpression induced mineralization in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament of the cervical spine. Calcif Tissue Int, 2011, 88(4): 263-271.
30.	孙树汉, 杨胜利. 单核苷酸多态性与复杂性状疾病. 第二军医大学学报, 2004, 25(2): 117-119.
31.	Kudo H, Furukawa K, Yokoyama T, et al. Genetic differences in the osteogenic differentiation potency according to the classification of ossification of the posterior longitudinal ligament of the cervical spine. Spine (Phila Pa 1976), 2011, 36(12): 951-957.

1. Barnes GL, Kostenuik PJ, Gerstenfeld LC, et al. Growth factor regulation of fracture repair. J Bone Miner Res, 1999, 14(11): 1805-1815.
2. Tanaka H, Nagai E, Murata H, et al. Involvement of bone morphogenic protein-2 in the pathological ossification process of the spinal ligament. Rheumatology (Oxford), 2001, 40(10): 1163-1168.
3. 陈棣, 叶伟胜. 骨形态发生蛋白的成骨功能及临床应用. 中华外科杂志, 1996, 34(10): 602-605.
4. Sampath T, Maliakal J, Hauschka P, et al. Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differention in vitro. J Biol Chem, 1992, 267(28): 20352-20362.
5. Inamasu J, Guiot BH, Sachs DC. Ossification of the posterior longitudinal ligament: an update on its biology, epidemiology, and natural history. Neurosurgery, 2006, 58(6): 1027-1039.
6. Wang H, Liu D, Yang Z, et al. Association of bone morphogenetic protein-2 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the spine and its severity in Chinese patients. Eur Spine J, 2008, 1(7): 956-964.
7. Wang H, Yang ZH, Liu DM, et al. Association between two polymorphisms of the bone morpho-genetic protein-2 gene with genetic susceptibility to ossification of the posterior longitudinal ligament of the cervical spine and its severity. Chin Med J (Engl), 2008, 121(18): 1806-1810.
8. Furushima K, Shimo-Onoda A, Maeda S, et al. Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine. J Bone Miner Res, 2002, 17(1): 128-137.
9. Meng XL, Wang H, Yang H, et al. T allele at site 6007 of bone morphogenetic protein-4 gene increases genetic susceptibility to ossification of the posterior longitudinal ligament in male Chinese Han population. Chin Med J (Engl), 2010, 123(18): 2537-2542.
10. 赵伟光, 谢延平, 闫亮, 等. 骨形态发生蛋白-4基因单核苷酸多态性与颈椎后纵韧带骨化症. 中国康复理论与实践, 2011, 17(1): 39-41.
11. Ren Y, Feng J, Liu ZZ, et al. A new haplotypein BMP4 implicated in ossification of the posterior longitudinal ligament (OPLL) in a Chinese population. J Orthop Res, 2012, 30(5): 748-756.
12. Yonemori K, Imamura T, Ishidou Y, et al. Bone morphogenetic protein receptors and activin receptors are highly expressed in ossified ligament tissues of patients with ossification of the posterior longitudinal ligament. Am J Pathol, 1997, 150(4): 1335-1347.
13. Freedman BI, Bowden DW, Ziegler JT, et al. Bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with inverse relationships between vascular calcification and BMD: the diabetes heart study. J Bone Miner Res, 2009, 24(10): 1719-1727.
14. Yan L, Zhao WG, Li JJ, et al. Linkage of three polymorphisms on chromosome 20p12 to ossification of the posterior longitudinal ligament of spine and its severity in Han Chinese patients. Chin Med J (Engl), 2010, 123(17): 2341-2346.
15. Chen D, Harris MA, Rossin G, et al. Bone morphogenetic protein 2 (BMP-2) enhances BMP-3, BMP-4, and bone cell differentiation marker gene expression during the induction of mineralized bone matrix formation in cultures of fetal rat calvarial osteoblasts. Calcif Tissue Int, 1997, 60(3): 283-290.
16. Miyazono K, Maeda S, Imamura T. BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev, 2005, 16(3): 251-263.
17. Tsai AD, Yeh LC, Lee JC. Effects of osteogenic protein-1 (OP-1, BMP-7) on gene expression in cultured medial collateral ligament cells. J Cell Biochem, 2003, 90(4): 777-791.
18. Stetler WR, La Marca F, Park P. The genetics of ossification of the posterior longitudinal ligament. Neurosurg Focus, 2011, 30(3): E7.
19. Li H, Jiang LS, Dai LY. High glucose potentiates collagen synthesis and bone morphogenetic protein-2-induced early osteoblast gene expression in rat spinal ligament cells. Endocrinology, 2010, 151(1): 63-74.
20. Baba H, Furusawa N, Fukuda M, et al. Potential role of streptozotocin in enhancing ossification of the posterior longitudinal ligament of the cervical spine in the hereditary spinal hyperostotic mouse (twy/twy). Eur J Histochem, 1997, 41(3): 191-202.
21. Yokosuka K, Park JS, Jimbo K, et al. Immunohistochemical demonstration of advanced glycation end products and the effects of advanced glycation end products in ossified ligament tissues in vitro. Spine (Phila Pa 1976), 2007, 32(11): E337-339.
22. 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 phosphat idylinositol 3-kinase. Spine (Phila Pa 1976), 2011, 33(22): 2394-2402.
23. Ikeda Y, Nakajima A, Aiba A, et al. Association between serum leptin and bone metabolic markers, and the development of heterotopic ossification of the spinal ligament in female patients with ossification of the posterior longitudinal ligament. Eur Spine J, 2011, 20(9): 1450-1458.
24. Tanno M, Furukawa KI, Ueyama K, et al. Unixial cyclic stretch induces osteogenic differention and synthesis of bone morphogenetic proteins of spine ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone, 2003, 33(4): 475-484.
25. Tsukamoto N, Maeda T, Miura H, et al. Repetitive tensile stress to rat caudal vertrbrae induing cartilage formation in the spinal ligaments: a possible role of mechanial stress in the development of ossification of the spinal ligaments. J Neurosurg Spine, 2006, 5(3): 234-242.
26. 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.
27. 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.
28. Ghosh-Choudhury N, Harris MA, Feng JQ, et al. Expression of the BMP2 gene during bone cell differentiation. Crit Rev Eukaryot Gene Expr, 1994, 4(2-3): 345-355.
29. Tanaka S, Kudo H, Asari T, et al. P2Y1 transient overexpression induced mineralization in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament of the cervical spine. Calcif Tissue Int, 2011, 88(4): 263-271.
30. 孙树汉, 杨胜利. 单核苷酸多态性与复杂性状疾病. 第二军医大学学报, 2004, 25(2): 117-119.
31. Kudo H, Furukawa K, Yokoyama T, et al. Genetic differences in the osteogenic differentiation potency according to the classification of ossification of the posterior longitudinal ligament of the cervical spine. Spine (Phila Pa 1976), 2011, 36(12): 951-957.

Chinese Journal of Reparative and Reconstructive Surgery

RESEARCH PROGRESS OF BONE MORPHOGENETIC PROTEIN AND LIABILITY OF OSSIFICATION OF POSTERIOR LONGITUDINAL LIGAMENT

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