GPR35 regulates osteogenesis via the Wnt/GSK3β/β-catenin signaling pathway

被引：23

作者：

Zhang, Yao ^{[1
]}

Shi, Tingwang ^{[1
]}

He, Yaohua ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Dept Orthopaed, Affiliated Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2021年 / 556卷

关键词：

GPR35; Osteoporosis; Osteogenesis; GSK3; beta; beta-Catenin;

D O I：

10.1016/j.bbrc.2021.03.084

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

It is well known that osteoporosis is a significant chronic disease with the increase of the aging population. Here, we report that expression of G protein-coupled receptor 35 (GPR35) in bone marrow mesenchymal stem cells (BMSCs) is suppressed in diagnosed osteoporosis patients and osteoporotic mice. The expression of GPR35 on BMSCs is enhanced during osteogenic differentiation. GPR35 knockout suppresses the proliferation and osteogenesis of BMSCs and deteriorates bone mass in both sham-treated and ovariectomized mice. Moreover, GPR35 deficiency reduces beta-catenin activity in BMSCs. In contrast, the overexpression of GPR35 contributes to these processes in BMSCs. Finally, using zaprinast, a synthetic GPR35 agonist, we show that zaprinast rescues OVX-induced bone loss and promotes bone generation in mice. Thus, GPR35 may as a new target and its agonist zaprinast may serve as a novel treatment for osteoporosis. (C) 2021 Elsevier Inc. All rights reserved.

引用

页码：171 / 178

页数：8

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