Apigenin alleviates osteoporosis by orchestrating SIRT1/HIF1α signaling in mesenchymal stem cells

Osteoporosis (OP) is a systemic skeletal disease characterized by reduced bone mass and a degenerative bone microarchitecture. Apigenin (API), a flavonoid derived mainly from celery, has been reported to be beneficial for the treatment of OP; however, the underlying mechanisms remain unclear. Moreover, the effects of API on bone-forming cells, including mesenchymal stem cells and osteoblasts, remain unclear. In the present study, we first determined that API treatment could promote bone formation, improve bone metabolism in ovariectomized (OVX) mice, and effectively ameliorate bone loss, as supported by micro-CT scanning and histological staining of mouse femurs. In vitro investigations have confirmed that API has a bidirectional regulatory effect on bone metabolism, promoteing osteogenic differentiation and inhibiting osteoclastogenesis. The further study displayed that the promotion of osteogenesis of bone marrow-derived mesenchymal stem cells from OVX mice mainly through regulating SIRT1 and its downstream HIF1α signaling. In summary, API treatment may be a novel and promising therapeutic strategy for the treatment of OP.