Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes
Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes
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DOI：
10.1016/j.devcel.2005.02.013
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发表时间：
2005-05-01
影响因子：
11.8
通讯作者：
Hartmann, C
中科院分区：
文献类型：
--
作者：
Hill, TP;Später, D;Hartmann, C
成骨细胞和软骨细胞参与了脊椎动物骨骼的构建，并被认为有别于常见的间充质前体--骨软骨前体。尽管已经确定了许多参与软骨细胞和成骨细胞分化的转录因子，但对控制这两种细胞的谱系决定的信号知之甚少。在这里，我们通过有条件地删除肢体和头部间充质中的β-连环蛋白，表明β-连环蛋白是成骨细胞系分化所必需的。缺乏β-连环蛋白的成骨细胞前体在分化过程中受阻，而是发育成软骨细胞。体外实验证明，这是成骨细胞前体中P-连环蛋白的细胞自主功能。此外，详细的体内和体外功能丧失和功能获得分析表明，β-连环素活性是抑制间充质细胞分化为Runx2和Sox9阳性骨骼前体所必需的，也是充分的。因此，规范的Wnt/β-catenin信号对骨骼谱系分化是必不可少的，阻止成骨细胞向软骨细胞的转分化。
Osteoblasts and chondrocytes are involved in building up the vertebrate skeleton and are thought to differentiate from a common mesenchymal precursor, the osteo-chondroprogenitor. Although numerous transcription factors involved in chondrocyte and osteoblast differentiation have been identified, little is known about the signals controlling lineage decisions of the two cell types. Here, we show by conditionally deleting beta-catenin in limb and head mesenchyme that beta-catenin is required for osteoblast lineage differentiation. Osteoblast precursors lacking beta-catenin are blocked in differentiation and develop into chondrocytes instead. In vitro experiments demonstrate that this is a cell-autonomous function of P-catenin in an osteoblast precursor. Furthermore, detailed in vivo and in vitro loss- and gain-of-function analyses reveal that beta-catenin activity is necessary and sufficient to repress the differentiation of mesenchymal cells into Runx2- and Sox9-positive skeletal precursors. Thus, canonical Wnt/beta-catenin signaling is essential for skeletal lineage differentiation, preventing transdifferentiation of osteoblastic cells into chondrocytes.