Osthole enhances the bone mass of senile osteoporosis and stimulates the expression of osteoprotegerin by activating β-catenin signaling

Introduction: Osthole has a potential therapeutic application for anti-osteoporosis. The present study verified whether osthole downregulates osteoclastogenesis via targeting OPG. Methods: In vivo, 12-month-old male mice were utilized to evaluate the effect of osthole on bone mass. In vitro, bone marrow stem cells (BMSCs) were isolated and extracted from 3-month-old OPG -/- mice and the littermates of OPG +/+ mice. calvaria osteoblasts were extracted from 3-day-old C57BL/6J mice or 3-day-old OPG -/- mice and the littermates of OPG +/+ mice. Results: Osthole significantly increased the gene and protein levels of OPG in primary BMSCs in a dose-dependent manner. The deletion of the OPG gene did not affect β-catenin expression. The deletion of the β-catenin gene inhibited OPG expression in BMSCs, indicating that osthole stimulates the expression of OPG via activation of β-catenin signaling. Conclusion: Osthole attenuates osteoclast formation by stimulating the activation of β-catenin-OPG signaling and could be a potential drug for the senile osteoporosis.