Dose-response estrogen promotes osteogenic differentiation via GPR40 (FFAR1) in murine BMMSCs.

摘要: Estrogen plays an essential role in bone formation, and estrogen modulation dysfunction is tightly associated with postmenopausal osteoporosis (PMOP). The underlying mechanisms of estrogen-mediated osteogenic differentiation have not been well defined. In this study, murine marrow mesenchymal stem cells were induced to undergo differentiation, gene expression analysis or GPR40 manipulation was performed. Bilateral ovariectomized sham-operated C57BL/6 mice administered agonist (GW9508) for mineral density analysis. We identified GPR40, a long chain unsaturated fatty acid receptor, be regulated by involved both in vivo in vitro. Mechanistically, the Wnt/β-catenin signaling pathway promote differentiation. Furthermore, GW9508 administration rescued estrogen-deficient loss, indicating receptor. To our knowledge, first study that provides evidence as positive regulator osteogenesis signaling. These results indicate may function endogenous promoter estrogen-induced through activation. Therefore, global population ages prevalence metabolic-related disorders, especially PMOP, increases, findings suggest key understanding link between fat. It also useful target treatment complications future.