RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation

被引：126

作者：

Chen, Xiao ^{[1
,2
]}

Zhi, Xin ^{[3
]}

Wang, Jun ^{[4
]}

Su, Jiacan ^{[1
]}

机构：

[1] Second Mil Med Univ, Shanghai Changhai Hosp, Dept Orthoped Trauma, Shanghai, Peoples R China

[2] Fudan Univ, Dept Chem, Shanghai, Peoples R China

[3] Second Mil Med Univ, Sch Basic Med Sci, Shanghai, Peoples R China

[4] Fudan Univ, Coll Life Sci, Shanghai, Peoples R China

来源：

BONE RESEARCH | 2018年 / 6卷

基金：

中国国家自然科学基金;

关键词：

POSTMENOPAUSAL OSTEOPOROSIS; DENOSUMAB EXPOSURE; OSTEOCLAST; WOMEN; DIFFERENTIATION; EXPRESSION; MIGRATION; RECEPTOR; MASS;

D O I：

10.1038/s41413-018-0035-6

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

RANKL signaling is essential for osteoclastogenesis. Its role in osteoblastic differentiation and bone formation is unknown. Here we demonstrate that RANK is expressed at an early stage of bone marrow mesenchymal stem cells (BMSCs) during osteogenic differentiation in both mice and human and decreased rapidly. RANKL signaling inhibits osteogenesis by promoting beta-catenin degradation and inhibiting its synthesis. In contrast, RANKL signaling has no significant effects on adipogenesis of BMSCs. Interestingly, conditional knockout of rank in BMSCs with Prx1-Cre mice leads to a higher bone mass and increased trabecular bone formation independent of osteoclasts. In addition, rank(flox/flox): Prx1-Cre mice show resistance to ovariectomy-(OVX) induced bone loss. Thus, our results reveal that RANKL signaling regulates both osteoclasts and osteoblasts by inhibition of osteogenic differentiation of BMSCs and promotion of osteoclastogenesis.

引用

页数：8

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