Ginsenoside F1 promotes osteoblast differentiation via BMP-SMAD pathway and stimulates bone formation in ovariectomy-induced osteoporosis

Osteoblasts are bone-building cells that drive osteogenesis by producing osteoid and promoting its mineralization during development and remodeling. Although ginsenosides from Panax species have been reported to enhance bone formation and inhibit resorption, the role of ginsenoside F1 on osteoblast differentiation and bone metabolism has not been defined. Here, we report a direct effect of ginsenoside F1 on osteoblast differentiation and bone formation in an osteoporotic model. Gene expression and protein induction analyses showed increased levels of osteogenic transcription factors in F1-induced bone marrow-derived mesenchymal stem cells (BMSCs) and primary osteoblasts compared to untreated cells. RNA-seq data analysis and molecular docking studies identified an association between bone morphogenetic protein receptor, type 1b (BMPR1b), and SMAD proteins for induction of osteoblast differentiation by F1 treatment. Furthermore, siRNA-mediated knockdown of BMPR1B attenuated inhibition of the downstream signaling of SMAD1/5/9 pathway, indicating that BMP-activated SMAD signaling is required for the pro-osteogenic action of F1. In addition, F1 alleviated the bone loss and increased bone mass in an ovariectomy-induced osteoporosis model in vivo . Collectively, these findings suggest that ginsenoside F1 enhances osteoblast differentiation and promotes bone formation under osteoporotic conditions, highlighting its therapeutic potential for disorders of bone metabolism.