Canonical Wnts and BMPs cooperatively induce osteoblastic differentiation through a GSK3β-dependent and β-catenin-independent mechanism
Canonical Wnts and BMPs cooperatively induce osteoblastic differentiation through a GSK3β-dependent and β-catenin-independent mechanism
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DOI：
10.1016/j.diff.2010.05.002
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发表时间：
2010-07-01
期刊：
影响因子：
2.9
通讯作者：
Katagiri, Takenobu
中科院分区：
文献类型：
--
作者：
Fukuda, Toru;Kokabu, Shoichiro;Katagiri, Takenobu
BMPs和Wnts在骨形成的调控中均发挥重要作用。我们研究了在C2 C12细胞的成骨分化中调节BMP和Wnts之间的串扰的分子机制。在BMP-4存在下，典型Wnt（Wnt 1和Wnt 3a）而非非典型Wnt（Wnt 5a和Wnt 11）协同刺激ALP活性。Wnt 3a和BMP-4协同刺激I型胶原和骨粘连蛋白的表达。然而，Wnt 3a没有刺激ALP活性，诱导的组成型活性BMP受体或Smad 1。Noggin和Dkk-1抑制BMP-4和Wnt 3a的协同作用，但Smad 7没有。β-连环蛋白的过表达不影响BMP-4诱导的ALP活性。相比之下，在BMP-4存在下，抑制或刺激GSK 3 β活性分别导致刺激或抑制ALP活性。总之，这些发现表明，骨形成蛋白和典型的Wnt可以调节成骨细胞分化，特别是在早期阶段，通过GSK 3 β依赖性，但β-连环蛋白的独立机制。(C)2010年国际分化学会。由爱思唯尔有限公司出版。保留所有权利。
Both BMPs and Wnts play important roles in the regulation of bone formation. We examined the molecular mechanism regulating cross-talk between BMPs and Wnts in the osteoblastic differentiation of C2C12 cells. Canonical Wnts (Wnt1 and Wnt3a) but not non-canonical Wnts (Wnt5a and Wnt11) synergistically stimulated ALP activity in the presence of BMP-4. Wnt3a and BMP-4 synergistically stimulated the expression of type I collagen and osteonectin. However, Wnt3a did not stimulate ALP activity that was induced by a constitutively active BMP receptor or Smad1. Noggin and Dkk-1 suppressed the synergistic effect of BMP-4 and Wnt3a, but Smad7 did not. Overexpression of beta-catenin did not affect BMP-4-induced ALP activity. By contrast, inhibition or stimulation of GSK3 beta activity resulted in either stimulation or suppression of ALP activity, respectively, in the presence of BMP-4. Taken together, these findings suggest that BMPs and canonical Wnts may regulate osteoblastic differentiation, especially at the early stages, through a GSK3 beta-dependent but beta-catenin-independent mechanism. (C) 2010 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.