Red ginseng-derived nanovesicles to modulate osteoblast and osteoclastogenesis for osteoporosis therapy.

Osteoporosis is a skeletal disorder characterized by an imbalance between bone formation and resorption, which leads to progressive bone loss and increased fracture risk. While current treatments either inhibit bone resorption or stimulate bone formation, their long-term use is associated with adverse effects, necessitating alternative therapeutic approaches. In this study, we explore the use of red ginseng-derived nanovesicles (RGNVs) as a biocompatible nanotherapeutic strategy for treating osteoporosis. The RGNVs were successfully isolated and characterized, revealing a lipid bilayer structure enriched in bioactive ginsenosides and functional proteins. In vitro, RGNVs enhanced osteoblast proliferation, differentiation, and mineralization while suppressing osteoclast differentiation and bone resorption by modulating the BMP-2/Smad and MAPK signaling pathways. In an ovariectomy-induced osteoporosis mouse model, oral administration of RGNVs significantly restored bone volume and mineral density, and biodistribution studies confirmed their preferential accumulation in the bone tissue. Systemic toxicity evaluation indicated no adverse effects, supporting the safety of RGNVs for therapeutic use. These findings suggest that RGNVs regulate bone remodeling through a dual mechanism, to stimulate bone formation and inhibit bone resorption, thereby offering a promising and well-tolerated approach for osteoporosis management.