Epimedin C prevents glucocorticoid-induced osteoporosis via balancing EphB4/EphrinB2 axis in a rodent model.

Purpose: To study the effect of Epimedin C on glucocorticoid (GC)-induced osteoporosis in a rodent model as well as its mechanism of action via balancing EphB4/EphrinB2 axis. Methods: Forty-eight C57BL/6 male mice were divided randomly into control, dexamethasone injection (DI), Epimedin C gavage (EG), and DI + EG groups. Micro-computed and hematoxylin-eosin staining was used to examine bone structure. The relationship between EphB4/EphrinB2 and osteoporosis was preliminarily verified by immunohistochemistry. Evidence of Epimedin C preventing the formation of GCinduced osteoclasts was determined by trap staining. Western blot analysis was conducted to determine the levels of EphrinB2, EphB4, Runx2, and LGR4 in mouse bone tissues. Results: In the DI group, morphological examination showed bone loss. The use of immunohistochemistry and Western blot studies showed that EphB4 levels decreased and EphrinB2 levels increased in DI group mice (p < 0.05). The morphological parameters of osteoporosis improved in mice of DI + EG group compared to that in DI group mice, while EphB4 levels were elevated and EphrinB2 levels decreased in comparison with the values in the DI group mice (p < 0.05). Conclusion: Epimedin C prevents bone loss by balancing the process of bone formation and remodeling bidirectionally. It affects bone metabolism by regulating protein levels of Runx2 and LGR4. However, the specific regulatory processes and targets of the anti-osteoporotic effect of Epimedin C regarding the EphB4/EphrinB2 signaling pathway still need to be confirmed. [ABSTRACT FROM AUTHOR]