Canonical Wnts and BMPs cooperatively induce osteoblastic differentiation through a GSK3β-dependent and β-catenin-independent mechanism

被引：53

作者：

Fukuda, Toru ^{[1
]}

Kokabu, Shoichiro ^{[1
]}

Ohte, Satoshi ^{[1
]}

Sasanuma, Hiroki ^{[1
]}

Kanomata, Kazuhiro ^{[1
]}

Yoneyama, Katsumi ^{[1
]}

Kato, Hitoshi ^{[2
]}

Akita, Masumi ^{[3
]}

Oda, Hiromi ^{[4
]}

Katagiri, Takenobu ^{[1
]}

机构：

[1] Saitama Med Univ, Res Ctr Genom Med, Div Pathophysiol, Hidaka, Saitama 3501241, Japan

[2] Saitama Med Univ, Saitama Med Ctr, Dept Hypertens & Nephrol, Kawagoe, Saitama 3508550, Japan

[3] Saitama Med Univ, Biomed Res Ctr, Div Morphol Sci, Moroyama, Saitama 3500495, Japan

[4] Saitama Med Univ, Dept Orthoped Surg, Moroyama, Saitama 3500495, Japan

来源：

DIFFERENTIATION | 2010年 / 80卷 / 01期

关键词：

BMP; Wnt; GSK3; beta; Osteoblastic differentiation; BONE MORPHOGENETIC PROTEIN-2; SIGNALING PATHWAY; RECEPTOR; MUTATION; IDENTIFICATION; CELLS; GENE; MASS; ID1; MINERALIZATION;

D O I：

10.1016/j.diff.2010.05.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：46 / 52

页数：7

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