Nuclear farnesoid X receptor protects against bone loss by driving osteoblast differentiation through stabilizing RUNX2.

ABSTRACT: The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis. Nuclear receptors (NRs) are now understood to be crucial in bone physiology and pathology. However, the function of the Farnesoid X receptor (FXR), a member of the NR family, in regulating bone homeostasis remains incompletely understood. In this study, in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells (BMSCs) and osteoblasts due to impaired osteoblast differentiation. Mechanistically, FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination, thereby promoting osteogenic activity in BMSCs. Moreover, activated FXR could directly bind to the Thoc6 promoter, sup

SUBMITTER: Dong Q 

PROVIDER: S-EPMC11782663 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature