Abstract
Background: Excessive activation of osteoclasts is an important cause of imbalance in bone remodeling, which further leads to pathological bone destruction. This is a clear feature of many osteolytic diseases, such as rheumatoid arthritis, osteoporosis, and osteolysis around the prosthesis. Based on the fact that many natural compounds have therapeutic potential for treating these diseases by suppressing osteoclast formation and function, we proved that α-mangostin, a natural compound isolated from mango, might be a promising choice. α-mangostin was described had anti‐inflammatory, anticancer and cardioprotective effects. Methods: We evaluated the therapeutic effect of α-mangostin in the process of osteoclast formation and bone resorption. The receptor activator of NF-κB ligand (RANKL) induces the formation of osteoclasts in vitro, and the potential pathways of α-mangostin to inhibit the differentiation and function of osteoclasts were explored. A mouse model of LPS‐induced calvarial osteolysis was establish. Subsequently, micro-CT, histology, etc. were used to evaluate the effect of α-mangostin in preventing inflammatory osteolysis.Results: In our study, we found that α-mangostin could inhibit RANKL-induced osteoclastogenesis and reduced osteoclast‐related gene expression in vitro. Besides, F-actin ring immunofluorescence and resorption pit assay indicated that α-mangostin can also destroy the function of osteoclast. Furthermore, α-mangostin achieved these effects by disrupting the activation of NF-κB/MAPKs signaling pathways. In vivo, our data revealed that α-mangostin could protect mouse calvarial from osteolysis. Conclusions: Together, our study demonstrates that α-mangostin exhibit the ability of inhibiting steoclastogenesis both in vitro and in vivo, and may be a potential option for treating osteoclast‐related diseases.