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BMP-5 expression increases during chondrocyte differentiation in vivo and in vitro and promotes proliferation and cartilage matrix synthesis in primary chondrocyte cultures

机译:Bmp-5表达在体内和体外软骨细胞分化期间增加,并促进原代软骨细胞培养物中的增殖和软骨基质合成。

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摘要

Bone morphogenetic proteins (BMPs) play pivotal roles in bone and cartilage growth and repair. Through phenotypes of short-ear (se) mice, which have BMP-5 mutations, a role for BMP-5 in some specific aspects of skeletogenesis and cartilage growth is known. This report examines BMP-5 expression in the growth plate and in differentiating cultures of primary chondrocytes, and the effects of addition of BMP-5 or its inhibition by anti-BMP-5 antibody in chondrocyte cultures. By laser capture microdissection and immunohistochemistry, we found that BMP-5 is expressed in proliferating zone (PZ) chondrocytes and that the expression increases sharply with hypertrophic differentiation. A similar pattern was observed in differentiating cultures of primary chondrocytes, with BMP-5 expression increasing as cells differentiated, in contrast to other BMPs. BMP-5 added to cultures increased cell proliferation early in the culture period and also stimulated cartilage matrix synthesis. Also, BMP-5 addition to the cultures activated phosphorylation of Smad 1/5/8 and p38 MAP kinase and caused increased nuclear accumulation of phospho-Smads. Anti-BMP-5 antibody inhibited the endogenous BMP-5, reducing cell proliferation and phospho-Smad nuclear accumulation. Together, the results demonstrate that BMP-5 is normally an important regulator of chondrocyte proliferation and differentiation. Whether other BMPs may compensate in BMP-5 loss-of-function mutations is discussed.
机译:骨形态发生蛋白(BMP)在骨骼和软骨的生长和修复中起关键作用。通过具有BMP-5突变的短耳(se)小鼠的表型,已知BMP-5在骨骼生成和软骨生长的某些特定方面的作用。该报告研究了软骨细胞在生长板和分化培养物中的BMP-5表达,以及软骨细胞培养物中BMP-5的添加或抗BMP-5抗体的抑制作用。通过激光捕获显微切割和免疫组织化学,我们发现BMP-5在增生区(PZ)软骨细胞中表达,并且该表达随着肥大性分化而急剧增加。在分化原代软骨细胞的培养物中观察到相似的模式,与其他BMP相比,随着细胞分化,BMP-5表达增加。向培养物中添加BMP-5可以在培养早期增加细胞增殖,还可以刺激软骨基质的合成。同样,向培养物中添加BMP-5可以激活Smad 1/5/8和p38 MAP激酶的磷酸化,并导致磷酸Smads的核积累增加。抗BMP-5抗体抑制内源性BMP-5,减少细胞增殖和磷酸Smad核积累。总之,结果表明BMP-5通常是软骨细胞增殖和分化的重要调节剂。讨论了其他BMP是否可以补偿BMP-5功能丧失突变。

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