Wnt/β-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis
Wnt/β-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis
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DOI：
10.1016/j.devcel.2005.03.016
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发表时间：
2005-05-01
影响因子：
11.8
通讯作者：
Yang, YZ
中科院分区：
文献类型：
--
作者：
Day, TF;Guo, XZ;Yang, YZ
软骨细胞和成骨细胞是骨骼系统中两种主要的细胞类型，它们由共同的间充质祖细胞分化而来。据信，成骨细胞分化在膜内成骨和软骨内成骨过程中受不同机制调控。我们发现，异位的经典Wnt信号传导会导致骨化增强以及软骨细胞形成受到抑制。相反，β - 连环蛋白（传导经典Wnt信号的关键成分）的基因失活会在膜内成骨和软骨内成骨过程中导致以成骨细胞分化为代价的软骨细胞异位形成。此外，在体外间充质祖细胞中β - 连环蛋白失活会在仅允许成骨细胞形成的条件下导致软骨细胞分化。我们的研究结果表明，无论区域位置或成骨机制如何，β - 连环蛋白对于决定间充质祖细胞是成为成骨细胞还是软骨细胞都至关重要。控制Wnt/β - 连环蛋白信号是软骨细胞和成骨细胞分化以及膜内成骨和软骨内成骨特化的一种共同分子机制。
Chondrocytes and osteoblasts are two primary cell types in the skeletal system that are differentiated from common mesenchymal progenitors. It is believed that osteoblast differentiation is controlled by distinct mechanisms in intramembranous and endochondral ossification. We have found that ectopic canonical Wnt signaling leads to enhanced ossification and suppression of chondrocyte formation. Conversely, genetic inactivation of beta-catenin, an essential component transducing the canonical Wnt signaling, causes ectopic formation of chondrocytes at the expense of osteoblast differentiation during both intramembranous and endochondral ossification. Moreover, inactivation of beta-catenin in mesenchymal progenitor cells in vitro causes chondrocyte differentiation under conditions allowing only osteoblasts to form. Our results demonstrate that R-catenin is essential in determining whether mesenchymal progenitors will become osteoblasts or chondrocytes regardless of regional locations or ossification mechanisms. Controlling Wnt/beta-catenin signaling is a common molecular mechanism underlying chondrocyte and osteoblast differentiation and specification of intramembranous and endochondral ossification.