Canonical Wnt/β-catenin signaling prevents osteoblasts from differentiating into chondrocytes

被引:944
作者
Hill, TP
Später, D
Taketo, MM
Birchmeier, W
Hartmann, C
机构
[1] Res Inst Mol Pathol, A-1030 Vienna, Austria
[2] Kyoto Univ, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan
[3] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany
关键词
D O I
10.1016/j.devcel.2005.02.013
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:727 / 738
页数:12
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