Cross-talk between Wnt signaling pathways in human mesenchymal stem cells leads to functional antagonism during osteogenic differentiation
Cross-talk between Wnt signaling pathways in human mesenchymal stem cells leads to functional antagonism during osteogenic differentiation
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DOI：
10.1002/jcb.21097
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发表时间：
2007-08-01
影响因子：
4
通讯作者：
Tuan, Rocky S.
中科院分区：
文献类型：
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作者：
Baksh, Dolores;Boland, Genevieve M.;Tuan, Rocky S.
WNT信号参与发育过程和成体干细胞的动态平衡。本研究分析了关键的Wnt信号调节因子(S)在骨髓间充质干细胞维持和成骨中的作用。我们特别关注低密度脂蛋白相关蛋白5(LRP5)、T细胞因子1(TCF1)和Frizzed(FZ)受体的参与，以及外源性、典型规范(Wnt3a)和非规范(Wnt5a)WNT的存在或不存在。在未分化的MSCs中，LRP5和TCF1介导典型的Wnt信号转导，导致增殖增加，并被Wnt3a协同增强。然而，LRP5过表达抑制成骨分化，Wnt3a进一步抑制了LRP5的成骨分化。Wnt5A不影响细胞增殖，但促进MSCs的成骨。有趣的是，Wnt5a抑制Wnt3a对MSCs的作用，而Wnt3a抑制Wnt5a介导的成骨促进作用。流式细胞术显示，LRP5的表达在未分化的和成骨的MSCs中引起了FZ受体的不同变化。综上所述，这些结果表明，Wnt信号串扰和与LRP5共受体的功能拮抗是MSC维持和分化的关键信号调节因子。J.细胞。生物化学。101：1109-1124,2007。(C)2007年Wiley-Liss，Inc.
Wnt signaling is involved in developmental processes and in adult stem cell homeostasis. This study analyzes the role(s) of key Wnt signaling mediators in the maintenance and osteogenesis of mesenchymal stern cells (MSCs). We focus specifically on the involvement of low-density lipoprotein-related protein 5 (LRP5), T-cell factor 1 (TCF1), and Frizzled (Fz) receptors, in the presence or absence of exogenous, prototypical canonical (Wnt3a), and non-canonical (Wnt5a) Wnts. In undifferentiated MSCs, LRP5 and TCF1 mediate canonical Wnt signal transduction, leading to increased proliferation, enhanced synergistically by Wnt3a. However, LRP5 overexpression inhibits osteogenic differentiation, further suppressed by Wnt3a. Wnt5a does not affect cell proliferation but enhances osteogenesis of MSCs. Interestingly, Wnt5a inhibits Wnt3a effects on MSCs, while Wnt3a suppresses Wnt5a-mediated enhancement of osteogenesis. Flow cytometry revealed that LRP5 expression elicits differential changes in Fz receptor profiles in undifferentiated versus osteogenic MSCs. Taken together, these results suggest that Wnt signaling crosstalk and functional antagonism with the LRP5 co-receptor are key signaling regulators of MSC maintenance and differentiation. J. Cell. Biochem. 101: 1109-1124, 2007. (C) 2007 Wiley-Liss, Inc.