Activation of BMPR1b-SMAD pathway by Ginsenoside F1 restores osteoblast function 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 can enhance bone formation and inhibit resorption, the role of ginsenoside F1 in osteoblast differentiation and bone metabolism has not been defined.

This study aimed to elucidate the molecular mechanism by which ginsenoside F1 promotes osteoblast differentiation and evaluate its therapeutic potential in an ovariectomy-induced osteoporosis model.

Bone marrow-derived mesenchymal stem cells and primary osteoblasts were treated with ginsenoside F1. Osteogenic differentiation was analyzed through gene and protein expression of key markers, including Runx2, Sp7 and Alpl. RNA-sequencing, molecular docking, and siRNA-mediated gene silencing were performed to identify and validate F1's target signaling pathway. The in vivo efficacy of F1 was assessed in ovariectomized mice using micro-computed tomography, histological staining, and biochemical assays.

Gene and protein expression analyses showed higher levels of osteogenic transcription factors in F1-induced osteoblasts than in untreated cells. RNA-sequencing analysis and molecular docking studies revealed an association between bone morphogenetic protein receptor type 1b (BMPR1b) and SMAD proteins important for mediating osteoblast differentiation following F1 induction. Furthermore, BMPR1B knockdown attenuated the inhibition of downstream SMAD1/5/9 signaling, indicating that BMP-activated SMAD signaling was required for the pre-osteogenic action of F1. In addition, F1 treatment increased bone mass in ovariectomy-induced osteoporosis.

Collectively, these findings suggest that ginsenoside F1 enhances osteoblast differentiation and promotes bone formation under osteoporotic conditions, highlighting its therapeutic potential for bone metabolism disorders.