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

First Author  Chen X Year  2018
Journal  Bone Res Volume  6
Pages  34 PubMed ID  30510839
Mgi Jnum  J:288018 Mgi Id  MGI:6415829
Doi  10.1038/s41413-018-0035-6 Citation  Chen X, et al. (2018) RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formation. Bone Res 6:34
abstractText  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.
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