BMP-6成骨機制和成骨效應的研究進展_《中國修復重建外科雜志》

作者：

許剛 , 張長春 , 周建生 , 黃震 , 孟紅亞

蚌埠醫學院第一附屬醫院骨科（安徽蚌埠，233004）;

關鍵詞：

BMP-6 成骨機制成骨效應

DOI：

10.7507/1002-1892.20130249

視頻：

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目的綜述BMP-6的成骨機制和成骨效應，為其進一步研究提供參考。方法廣泛查閱近年國內外有關BMP-6成骨機制及其在動物實驗中成骨效應的文獻，并進行歸納總結。結果 BMP-6由骨基質產生，通過Smad蛋白信號轉導途徑將成骨信號轉導至BMSCs，誘導其向成骨、成軟骨方向分化，并在骨和軟骨的發育成熟過程中起重要作用；BMP-6還與多種骨病（如骨折、骨質疏松、骨腫瘤）有密切關系。結論對BMP-6的深入研究有望為臨床治療骨折不愈合、骨關節炎、骨質疏松癥等相關骨病提供一條新途徑。

引用本文： 許剛,張長春,周建生,黃震,孟紅亞. BMP-6成骨機制和成骨效應的研究進展. 中國修復重建外科雜志, 2013, 27(9): 1144-1147. doi: 10.7507/1002-1892.20130249 復制

1.	Moghaddam A, Elleser C, Biglari B, et al. Clinical application of BMP-7 in long bone non-unions. Arch Orthop Trauma Surg, 2010, 130(1): 71-76.
2.	Li JZ, Li H, Sasaki T, et al. Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat. Gene Ther, 2003, 10(20): 1735-1743.
3.	何煥玲, 李星星, 賴天霞, 等. BMP-2、-3、-6和-12在骨肉瘤細胞株中的表達. 中國組織化學與細胞化學雜志, 2007, 16(2): 134-137.
4.	Goumans MJ, Mummery C. Functional anaysis of the TGFbeta receptor/Smad pathway through gene ablation in mice. Int J Dev Biol, 2000, 44(3): 253-265.
5.	Vukicevic S, Grgurevic L. BMP-6 and mesenchymal stem cell differentiation. Cytokine Growth Factor Rev, 2009, 20(5-6): 441-448.
6.	Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors, 2004, 22(4): 233-241.
7.	程宗生, 關鍵. 骨形態發生蛋白/Smad信號轉導機制及其對離心力刺激的響應. 國際口腔醫學雜志, 2009, 36(3): 335-337.
8.	楊尊. 低強度脈沖超聲波對人類牙周膜細胞骨形成蛋白BMP成骨調控機制的初步研究. 重慶: 重慶醫科大學, 2011.
9.	Sheu SY, Tsai CC, Sun JS, et al. Stimulatory effect of puerarin on bone formation through co-activation of nitric oxide and bone morphogenetic protein-2/mitogen-activated protein kinases pathways in mice. Chin Med J, 2012, 125(20): 3646-3653.
10.	Li C, Yang X, He Y, et al. Bone morphogenetic protein-9 induces osteogenic differentiation of rat dental follicle stem cells in P38 and ERK1/2 MAPK dependent manner. Int J Med Sci, 2012, 9(10): 862-871.
11.	Seamon J, Wang X, Cui F, et al. Adenoviral delivery of the VEGF and BMP-6 genes to rat mesenchymal stem cells potentiates osteogenesis. Bone Marrow Res, 2013, 2013: 737580.
12.	Mizrahi O, Shevn D, Tawackoli W, et al. BMP-6 is more efficient in bone formation than BMP-2 when overexpressed in mesenchymal stem cells. Gene Ther, 2013, 20(4): 370-377.
13.	Visser R, Pilar M, Santos-Ruiz L, et al. Basic fibroblast factor enhances the osteogenic differentiation induced by bone morphogenetic protein-6 in vitro and in vivo. Cytokine, 2012, 58(1): 27-33.
14.	Zachos TA, Shiekls KM, Bertone AL. Gene-mediated oeteogenic differentiation of stem cells by bone morphogentic proteins-2 or -6. J Orthop Res, 2006, 24(6): 1279-1291.
15.	Sheyn D, Kallai L, Tawackoli W, et al. Gene-modified adult stem cells regenerate vertebral bone defect in a rat model. Mol Pharm, 2011, 8(5): 1592-1601.
16.	Perry MJ, Mc Dougall KE, Hou SC, et al. Impaired growth plate fuction in bmp-6 null mice. Bone, 2008, 42(1): 216-225.
17.	Choi S, Cho TJ, Kwon SK, et al. Chondrogenesis of periodontal ligament stem cells by transforming growth factor-β3 and bone morphogenetic protein-6 in a normal healthy impacted third molar. Int J Oral Sci, 2013, 5(1): 7-13.
18.	Kayaba?i GK, Aydin RS, Gümü?derelio?lu M. In vitro chondrogenesis by BMP6 gene therapy. J Biomed Mater Res A, 2012, 101(5): 1353-1361.
19.	de Mara CS, Duarte AS, Sartori-Cintra AR, et al. Chondrogenesisi from umbilical cord blood cells stimulated with BMP-2 and BMP-6. Rheumatol Int, 2013, 33(1): 121-128.
20.	Nilsson O, Parker EA, Hegde A, et al. Gradients in bone morphogenetic protein-related gene expression across the growth plate. J Endocrinol, 2007, 193(1): 75-84.
21.	Menendez MI, Clark DJ, Carlton M, et al. Direct delayed human adnoviral BMP-2 or BMP-6 gene therapy for bone and cartilage regeneration in a pony osteochondral model. Osteoarthritis Cartilage, 2011, 19(8): 1066-1075.
22.	Fischerauer EE, Manninger M, Seles M, et al. BMP-6 and BMPR-1a are up-regulateded in the growth plate of the fractured tibia. J Orthop Res, 2013, 31(3): 357-363.
23.	Kemmis CM, Vahdati A, Weiss HE, et al. Bone morphogenetic protein 6 drives both osteogenesis and chondrogenesis in murine adipose-derived mesenchymal cells depending on culture conditions. Biochem Biophys Res Commun, 2010, 401(1): 20-25.
24.	Song K, Krause C, Shi S, et al. Identification of a key residue mediating bone morphogenetic protein (BMP)-6 resistance to noggin inhibition allows for engineered BMPs with superior agonist activity. J Biol Chem, 2010, 285(16): 12169-12180.
25.	Sinic P, Culej JB, Orlic I, et al. Systemically administered bone morphogenetic protein-6 restores bone in aged ovariectomized rats by increasing bone formation and suppressing bone resorption. J Biol Chem, 2006, 281(35): 25509-25521.
26.	尚德陽. 腎虛骨質疏松癥大鼠骨、腎、下丘腦組織BMP6/BMP7、Smurf1/Smurf2的mRNA及其蛋白表達的實驗研究. 沈陽: 遼寧中醫藥大學, 2008.
27.	Brkljacic J, Pauk M, et al. Exogenous heparin binds and inhibits bone morphogenetic protein 6 biological activity. Int Orthop, 2013, 37(3): 529-541.
28.	Hashida Y, Nemoto Y, Imajoh M, et al. Promoter methylation of the bone morphogenetic protein 6 gene in multiple myeloma. Oncol Rep, 2012, 27(3): 825-830.
29.	Yuen HF, McCrudden CM, Grills C, et al. Combinatorial use of bone morphogenetic protein 6, noggin and SOST significantly predicts cancer progression. Cancer Sci, 2012, 103(6): 1145-1154.

1. Moghaddam A, Elleser C, Biglari B, et al. Clinical application of BMP-7 in long bone non-unions. Arch Orthop Trauma Surg, 2010, 130(1): 71-76.
2. Li JZ, Li H, Sasaki T, et al. Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat. Gene Ther, 2003, 10(20): 1735-1743.
3. 何煥玲, 李星星, 賴天霞, 等. BMP-2、-3、-6和-12在骨肉瘤細胞株中的表達. 中國組織化學與細胞化學雜志, 2007, 16(2): 134-137.
4. Goumans MJ, Mummery C. Functional anaysis of the TGFbeta receptor/Smad pathway through gene ablation in mice. Int J Dev Biol, 2000, 44(3): 253-265.
5. Vukicevic S, Grgurevic L. BMP-6 and mesenchymal stem cell differentiation. Cytokine Growth Factor Rev, 2009, 20(5-6): 441-448.
6. Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors, 2004, 22(4): 233-241.
7. 程宗生, 關鍵. 骨形態發生蛋白/Smad信號轉導機制及其對離心力刺激的響應. 國際口腔醫學雜志, 2009, 36(3): 335-337.
8. 楊尊. 低強度脈沖超聲波對人類牙周膜細胞骨形成蛋白BMP成骨調控機制的初步研究. 重慶: 重慶醫科大學, 2011.
9. Sheu SY, Tsai CC, Sun JS, et al. Stimulatory effect of puerarin on bone formation through co-activation of nitric oxide and bone morphogenetic protein-2/mitogen-activated protein kinases pathways in mice. Chin Med J, 2012, 125(20): 3646-3653.
10. Li C, Yang X, He Y, et al. Bone morphogenetic protein-9 induces osteogenic differentiation of rat dental follicle stem cells in P38 and ERK1/2 MAPK dependent manner. Int J Med Sci, 2012, 9(10): 862-871.
11. Seamon J, Wang X, Cui F, et al. Adenoviral delivery of the VEGF and BMP-6 genes to rat mesenchymal stem cells potentiates osteogenesis. Bone Marrow Res, 2013, 2013: 737580.
12. Mizrahi O, Shevn D, Tawackoli W, et al. BMP-6 is more efficient in bone formation than BMP-2 when overexpressed in mesenchymal stem cells. Gene Ther, 2013, 20(4): 370-377.
13. Visser R, Pilar M, Santos-Ruiz L, et al. Basic fibroblast factor enhances the osteogenic differentiation induced by bone morphogenetic protein-6 in vitro and in vivo. Cytokine, 2012, 58(1): 27-33.
14. Zachos TA, Shiekls KM, Bertone AL. Gene-mediated oeteogenic differentiation of stem cells by bone morphogentic proteins-2 or -6. J Orthop Res, 2006, 24(6): 1279-1291.
15. Sheyn D, Kallai L, Tawackoli W, et al. Gene-modified adult stem cells regenerate vertebral bone defect in a rat model. Mol Pharm, 2011, 8(5): 1592-1601.
16. Perry MJ, Mc Dougall KE, Hou SC, et al. Impaired growth plate fuction in bmp-6 null mice. Bone, 2008, 42(1): 216-225.
17. Choi S, Cho TJ, Kwon SK, et al. Chondrogenesis of periodontal ligament stem cells by transforming growth factor-β3 and bone morphogenetic protein-6 in a normal healthy impacted third molar. Int J Oral Sci, 2013, 5(1): 7-13.
18. Kayaba?i GK, Aydin RS, Gümü?derelio?lu M. In vitro chondrogenesis by BMP6 gene therapy. J Biomed Mater Res A, 2012, 101(5): 1353-1361.
19. de Mara CS, Duarte AS, Sartori-Cintra AR, et al. Chondrogenesisi from umbilical cord blood cells stimulated with BMP-2 and BMP-6. Rheumatol Int, 2013, 33(1): 121-128.
20. Nilsson O, Parker EA, Hegde A, et al. Gradients in bone morphogenetic protein-related gene expression across the growth plate. J Endocrinol, 2007, 193(1): 75-84.
21. Menendez MI, Clark DJ, Carlton M, et al. Direct delayed human adnoviral BMP-2 or BMP-6 gene therapy for bone and cartilage regeneration in a pony osteochondral model. Osteoarthritis Cartilage, 2011, 19(8): 1066-1075.
22. Fischerauer EE, Manninger M, Seles M, et al. BMP-6 and BMPR-1a are up-regulateded in the growth plate of the fractured tibia. J Orthop Res, 2013, 31(3): 357-363.
23. Kemmis CM, Vahdati A, Weiss HE, et al. Bone morphogenetic protein 6 drives both osteogenesis and chondrogenesis in murine adipose-derived mesenchymal cells depending on culture conditions. Biochem Biophys Res Commun, 2010, 401(1): 20-25.
24. Song K, Krause C, Shi S, et al. Identification of a key residue mediating bone morphogenetic protein (BMP)-6 resistance to noggin inhibition allows for engineered BMPs with superior agonist activity. J Biol Chem, 2010, 285(16): 12169-12180.
25. Sinic P, Culej JB, Orlic I, et al. Systemically administered bone morphogenetic protein-6 restores bone in aged ovariectomized rats by increasing bone formation and suppressing bone resorption. J Biol Chem, 2006, 281(35): 25509-25521.
26. 尚德陽. 腎虛骨質疏松癥大鼠骨、腎、下丘腦組織BMP6/BMP7、Smurf1/Smurf2的mRNA及其蛋白表達的實驗研究. 沈陽: 遼寧中醫藥大學, 2008.
27. Brkljacic J, Pauk M, et al. Exogenous heparin binds and inhibits bone morphogenetic protein 6 biological activity. Int Orthop, 2013, 37(3): 529-541.
28. Hashida Y, Nemoto Y, Imajoh M, et al. Promoter methylation of the bone morphogenetic protein 6 gene in multiple myeloma. Oncol Rep, 2012, 27(3): 825-830.
29. Yuen HF, McCrudden CM, Grills C, et al. Combinatorial use of bone morphogenetic protein 6, noggin and SOST significantly predicts cancer progression. Cancer Sci, 2012, 103(6): 1145-1154.

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BMP-6成骨機制和成骨效應的研究進展

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BMP-6成骨機制和成骨效應的研究進展

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