Involvement of endogenous bone morphogenetic protein (BMP)2 and BMP6 in bone formation
Involvement of endogenous bone morphogenetic protein (BMP)2 and BMP6 in bone formation
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DOI：
10.1074/jbc.m505166200
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发表时间：
2005-10-21
影响因子：
4.8
通讯作者：
Chung, UG
中科院分区：
文献类型：
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作者：
Kugimiya, F;Kawaguchi, H;Chung, UG
尽管积累的证据表明骨形态发生蛋白（BMPs）在体外和体内外源作用下具有骨合成代谢作用，但内源BMPs在骨形成过程中的作用仍有待阐明。本研究初步研究了bmp在小鼠长骨中的表达模式，发现BMP2和BMP6是诱导软骨内成骨的增生性软骨细胞中表达的主要亚型。然后，我们通过生成化合物缺乏小鼠（Bmp2 +/-; Bmp6 -/-）来检测这些bmp组合在体内骨形成中的作用。在生理条件下，与野生型（WT）仔鼠相比，这些小鼠在观察期间表现出中度的生长迟缓，直至52周龄。胎儿和成年化合物缺乏小鼠均显示骨小梁体积减少，骨形成受到抑制，但骨吸收正常，而单一缺陷小鼠（Bmp2 +/-或Bmp6 -/-）则没有。当股骨中轴发生骨折并分析骨愈合情况时，软骨内骨形成，而不是膜内骨形成，因复合缺乏而受损。然而，在骨髓细胞培养中，在外源BMP2存在或不存在的情况下，WT和化合物缺陷细胞之间的成骨分化没有差异。因此，我们得出结论，内源性BMP2和BMP6在生理和病理条件下共同在骨形成中发挥关键作用。
Although accumulated evidence has shown the bone anabolic effects of bone morphogenetic proteins ( BMPs) that were exogenously applied in vitro and in vivo, the roles of endogenous BMPs during bone formation remain to be clarified. This study initially investigated expression patterns of BMPs in the mouse long bone and found that BMP2 and BMP6 were the main subtypes expressed in hypertrophic chondrocytes that induce endochondral bone formation. We then examined the involvement of the combination of these BMPs in bone formation in vivo by generating the compound-deficient mice ( Bmp2 +/-; Bmp6 -/-). Under physiological conditions, these mice exhibited moderate growth retardation compared with the wild- type ( WT) littermates during the observation period up to 52 weeks of age. Both the fetal and adult compound- deficient mice showed a reduction in the trabecular bone volume with suppressed bone formation, but normal bone resorption, whereas the single deficient mice ( Bmp2 +/- or Bmp6 -/-) did not. When a fracture was created at the femoral midshaft and the bone healing was analyzed, the endochondral bone formation, but not intramembranous bone formation, was impaired by the compound deficiency. In the cultures of bone marrow cells, however, there was no difference in osteogenic differentiation between WT and compounddeficient cells in the presence or absence of the exogenous BMP2. We thus concluded that endogenous BMP2 and BMP6 cooperatively play pivotal roles in bone formation under both physiological and pathological conditions.