Tumor necrosis factor alpha suppresses osteogenic differentiation of MSCs by inhibiting semaphorin 3B via Wnt/β-catenin signaling in estrogen-deficiency induced osteoporosis

被引：53

作者：

Sang, Chenglin ^{[1
,2
,3
]}

Zhang, Yongxian ^{[2
,3
]}

Chen, Fangjing ^{[2
,3
]}

Huang, Ping ^{[1
]}

Qi, Jin ^{[1
]}

Wang, Pingshan ^{[2
,3
]}

Zhou, Qi ^{[1
]}

Kang, Hui ^{[1
]}

Cao, Xuecheng ^{[2
,3
]}

Guo, Lei ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Key Lab Bone & Joint Dis, Shanghai Inst Orthopaed & Traumatol, Shanghai Ruijin Hosp,Sch Med, Shanghai 200025, Peoples R China

[2] Second Mil Med Univ, Dept Orthopaed, Jinan Clin Med Coll, 25 Shifan Rd, Jinan 250031, Peoples R China

[3] Jinan Mil Command, Dept Orthaoped, Gen Hosp, Jinan 250031, Shandong, Peoples R China

来源：

BONE | 2016年 / 84卷

基金：

中国国家自然科学基金;

关键词：

Osteogenesis; TNF-alpha; Wnt/beta-catenin signaling; MSCs; Semaphorin3B; MESENCHYMAL STEM-CELLS; BONE-MARROW; PROMOTES OSTEOCLASTOGENESIS; BETA-CATENIN; OSTEOBLASTS; EXPRESSION; RECEPTORS;

D O I：

10.1016/j.bone.2015.12.012

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The proinflammatory cytokines, especially tumor necrosis factor alpha (TNF-alpha), have been shown to inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and bone formation in estrogen-deficiency-induced osteoporosis, but the mechanisms of TNF-alpha impaired bone formation remain poorly understood. Semaphorins have been shown to regulate cell growth, cell migration, and cell differentiation in a variety of tissues, including bone tissue. Here, we identified a novel mechanism whereby TNF-alpha, suppressing Semaphorin3B expression contributes to estrogen-deficiency-induced osteoporosis. In this study, we found that TNF-alpha could decrease Semaphorin3B expression in osteogenic differentiation of MSCs. Overexpression of Semaphorin3B in MSCs attenuated the inhibitory effects of TNF-alpha. on MSCs proliferation and osteoblastic differentiation. Mechanistically, activation of the Wnt/beta-catenin signaling markedly rescued TNF-alpha-inhibited Semaphorin3B expression, suggesting that Wnt/beta-catenin signaling was involved in the regulation of Semaphorin3B expression by TNF-alpha. Taken together, our results revealed a novel function for Semaphorin3B and suggested that suppressed Semaphorin3B may contribute to impaired bone formation by elevated TNF-alpha in estrogen-deficiency-induced osteoporosis. This study may indicate a therapeutic target gene of Semaphorin3B for osteoporosis. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：78 / 87

页数：10

共 39 条

[31] Mechanisms of sex steroid effects on bone [J].