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

Abstract

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. Abbreviations used: α-MAG: α-mangostin, RANKL: Receptor activator of nuclear factor-κB ligand, ERK: Extracellular signal-regulated kinase, JNK: c-Jun N-terminal kinase, ANI: Anisomycin, M-CSF: Macrophage colony-stimulating factor, MAPK: Mitogen-activated protein kinase, IκBα: Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha, NFATc1: Nuclear factor of activated T cells c1, TRAP: Tartrate-resistant acid phosphatase, SEM: Scanning electron microscope, CTSK: Cathepsin K, CTR: Calcitonin receptor, DC-STAMP: Dendritic cell-specific transmembrane protein, TRAF6: Tumor necrosis factor receptor-associated factor 6, AP-1: Activator protein-1