Inhibition of adipocytogenesis by canonical WNT signaling in human mesenchymal stem cells

被引：38

作者：

Shen, Longxiang ^{[1
]}

Glowacki, Julie ^{[1
]}

Zhou, Shuanhu ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA

来源：

EXPERIMENTAL CELL RESEARCH | 2011年 / 317卷 / 13期

关键词：

WNT; Human mesenchymal stem cells; Adipocytogenesis; beta-catenin; SB-216763; Gene silencing; MARROW STROMAL CELLS; ACTIVATED RECEPTOR-GAMMA; BONE-MARROW; BETA-CATENIN; GENE-EXPRESSION; ADIPOCYTE DIFFERENTIATION; PPAR-GAMMA; ADIPOGENESIS; OSTEOBLASTOGENESIS; PREADIPOCYTES;

D O I：

10.1016/j.yexcr.2011.05.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The WNT signaling pathway plays important roles in the self-renewal and differentiation of mesenchymal stem cells (MSCs). Little is known about WNT signaling in adipocyte differentiation of human MSCs. In this study, we tested the hypothesis that canonical and non-canonical WNTs differentially regulate in vitro adipocytogenesis in human MSCs. The expression of adipocyte gene PPAR gamma 2, lipoprotein lipase, and adipsin increased during adipocytogenesis of hMSCs. Simultaneously, the expression of canonical WNT2, 10B, 13, and 14 decreased, whereas non-canonical WNT4 and 11 increased, and WNT5A was unchanged. A small molecule WNT mimetic, SB-216763, increased accumulation of beta-catenin protein, inhibited induction of WNT4 and 11 and inhibited adipocytogenesis. In contrast, knockdown of beta-catenin with siRNA resulted in spontaneous adipocytogenesis. These findings support the view that canonical WNT signaling inhibits and non-canonical WNT signaling promotes adipocytogenesis in adult human marrow-derived mesenchymal stem cells. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：1796 / 1803

页数：8

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