• 1南開大學人民醫(yī)院脊柱外科（天津，300121）;;
  • 2天津醫(yī)科大學 天津市人民醫(yī)院脊柱外科;

目的綜述BMP與后縱韌帶骨化癥（ossification of the posterior longitudinal ligament，OPLL）易患性的研究進展。 方法查閱近年國內(nèi)外有關(guān)BMP與OPLL易患性的相關(guān)參考文獻并進行總結(jié)。 結(jié)果BMP基因的單核苷酸多態(tài)性（single nucleotide polymorphisms，SNPs）產(chǎn)生微效累加效應增加對OPLL的易感性，多種環(huán)境因素可通過增加BMPs基因的表達，促進OPLL的發(fā)生、發(fā)展。 結(jié)論BMPs易感基因的SNPs可促進個體對OPLL的易感性，SNPs的累加效應及與環(huán)境因素的相互作用則可影響個體對OPLL易患性的高低。

引用本文： 方釗,孫天威,Sandip Kumar Yadav. BMP與后縱韌帶骨化癥易患性的研究進展. 中國修復重建外科雜志, 2012, 26(10): 1255-1258. doi: 復制

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. 陳棣, 葉偉勝. 骨形態(tài)發(fā)生蛋白的成骨功能及臨床應用. 中華外科雜志, 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. 趙偉光, 謝延平, 閆亮, 等. 骨形態(tài)發(fā)生蛋白-4基因單核苷酸多態(tài)性與頸椎后縱韌帶骨化癥. 中國康復理論與實踐, 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. 譚炳毅, 賈連順, 王海燕, 等. 應力刺激對于后縱韌帶骨化因子的影響. 中國矯形外科雜志, 2006, 14(13): 1013-1015.
27. 向選平, 金濤, 王華, 等. 手術(shù)刺激對腰椎后縱韌帶內(nèi)BMP-2及BMP-7 mRNA表達的影響. 中國現(xiàn)代醫(yī)學雜志, 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. 孫樹漢, 楊勝利. 單核苷酸多態(tài)性與復雜性狀疾病. 第二軍醫(yī)大學學報, 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. 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. 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. 3. 陳棣, 葉偉勝. 骨形態(tài)發(fā)生蛋白的成骨功能及臨床應用. 中華外科雜志, 1996, 34(10): 602-605.
  4. 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. 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. 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. 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. 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. 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. 10. 趙偉光, 謝延平, 閆亮, 等. 骨形態(tài)發(fā)生蛋白-4基因單核苷酸多態(tài)性與頸椎后縱韌帶骨化癥. 中國康復理論與實踐, 2011, 17(1): 39-41.
  11. 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. 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. 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. 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. 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. 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. 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. 18. Stetler WR, La Marca F, Park P. The genetics of ossification of the posterior longitudinal ligament. Neurosurg Focus, 2011, 30(3): E7.
  19. 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. 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. 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. 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. 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. 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. 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. 26. 譚炳毅, 賈連順, 王海燕, 等. 應力刺激對于后縱韌帶骨化因子的影響. 中國矯形外科雜志, 2006, 14(13): 1013-1015.
  27. 27. 向選平, 金濤, 王華, 等. 手術(shù)刺激對腰椎后縱韌帶內(nèi)BMP-2及BMP-7 mRNA表達的影響. 中國現(xiàn)代醫(yī)學雜志, 2010, 20(6): 858-864.
  28. 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. 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. 30. 孫樹漢, 楊勝利. 單核苷酸多態(tài)性與復雜性狀疾病. 第二軍醫(yī)大學學報, 2004, 25(2): 117-119.
  31. 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.