RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation
Open Access
- 27 November 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Bone Research
- Vol. 6 (1), 1-8
- https://doi.org/10.1038/s41413-018-0035-6
Abstract
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 β-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, rankflox/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.Keywords
Funding Information
- National Natural Science Foundation of China (91749204, 81771491, 81501052)
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