Alpha-mangostin Suppresses Receptor Activator Nuclear Factor-κB Ligand-induced Osteoclast Formation and Bone Resorption in RAW264.7 Cells by Inhibiting the Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase Signaling

Background: Excessive osteoclast formation and over‑activated function lead to a series of osteoclast‑related diseases. Suppression of osteoclastogenesis is likely to be an effective means for the treatment of these diseases. Objective: In this study, we investigated the effects of alpha‑mangostin (α‑MAG), a natural compound derived from Garcinia mangostana, on osteoclast formation and function in RAW264.7 cells. Materials and Methods: Different concentrations of α‑MAG were used to explore its effects on receptor activator of nuclear factor‑κB ligand (RANKL)‑induced osteoclastogenesis and further, we investigated the mechanism by Western Blotting. Results: The study revealed that α‑MAG attenuated RANKL‑induced osteoclastogenesis. Moreover, the effects were confirmed to be caused by the suppression of the phosphorylation of the extracellular signal‑regulated kinase (ERK) and c‑Jun N‑terminal kinase (JNK) signaling and this inhibitory effect could be rescued by the administration of the JNK and p38 agonist anisomycin. Conclusion: The study results demonstrated that α‑MAG could impair RANKL‑induced osteoclastogenesis by inhibiting the ERK and JNK signaling pathways in RAW264.7 cells.