Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo
Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo
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DOI：
10.1073/pnas.0500031102
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发表时间：
2005-04-05
影响因子：
11.1
通讯作者：
Lyons, KM
中科院分区：
文献类型：
--
作者：
Yoon, BS;Ovchinnikov, DA;Lyons, KM
以前的研究已经证明骨形态发生蛋白（BMP）的能力，以促进软骨分化在体外。然而，BMP信号在软骨形成过程中的体内作用尚不清楚。我们在这里报告，BMP信号是必不可少的早期软骨形成的多个方面。尽管软骨中缺乏1型受体Bmpr 1a或Bmpr 1b的小鼠能够形成完整的软骨元件，但双突变体会发展为严重的全身性软骨发育不良。大多数通过软骨内骨化形成的骨骼元素都不存在，形成的骨骼元素是不成熟的。在双突变体中形成的少数软骨凝聚在软骨细胞前状态中被延迟，并且从未形成有组织的生长板。突变体浓缩物的尺寸减小是由于细胞凋亡增加和增殖减少。此外，软骨特异性细胞外基质蛋白的表达在突变元件中严重减少。我们证明，这种缺陷的软骨细胞分化可以归因于缺乏Sox 9，L-Sox 5，Sox 6的表达在precartilaginous缩合双突变体。总之，我们的研究表明，BMPR 1A和BMPR 1B在早期软骨形成过程中是功能冗余的，BMP信号是体内软骨细胞增殖、存活和分化所必需的。
Previous studies have demonstrated the ability of bone morphogenetic proteins (BMPs) to promote chondrogenic differentiation in vitro. However, the in vivo role of BMP signaling during chondrogenesis has been unclear. We report here that BMP signaling is essential for multiple aspects of early chondrogenesis. Whereas mice deficient in type 1 receptors Bmpr1a or Bmpr1b in cartilage are able to form intact cartilaginous elements, double mutants develop a severe generalized chondrodysplasia. The majority of skeletal elements that form through endochondral ossification are absent, and the ones that form are rudimentary. The few cartilage condensations that form in double mutants are delayed in the prechondrocytic state and never form an organized growth plate. The reduced size of mutant condensations results from increased apoptosis and decreased proliferation. Moreover, the expression of cartilage-specific extracellular matrix proteins is severely reduced in mutant elements. We demonstrate that this defect in chondrocytic differentiation can be attributed to lack of Sox9, L-Sox5, and Sox6 expression in precartilaginous condensations in double mutants. In summary, our study demonstrates that BMPR1A and BMPR1B are functionally redundant during early chondrogenesis and that BMP signaling is required for chondrocyte proliferation, survival, and differentiation in vivo.