α-Mangostin inhibits LPS-induced bone resorption by restricting osteoclastogenesis via NE-κB and MAPK signaling

Background: Excessive osteoclast activation is an important cause of imbalanced bone remodeling that leads to pathological bone destruction. This is a clear feature of many osteolytic diseases such as rheumatoid arthritis, osteoporosis, and osteolysis around prostheses. Because many natural compounds have therapeutic potential for treating these diseases by suppressing osteoclast formation and function, we hypothesized that alpha-mangostin, a natural compound isolated from mangosteen, might be a promising treatment as it exhibits anti-inflammatory, anticancer, and cardioprotective effects. Methods: We evaluated the therapeutic effect of alpha-mangostin on the processes of osteoclast formation and bone resorption. The receptor activator of nuclear factor-kappa B (NF-kappa B) ligand (RANKL) induces osteoclast formation in vitro, and potential pathways of alpha-mangostin to inhibit osteoclast differentiation and function were explored. A mouse model of lipopolysaccharide-induced calvarial osteolysis was established. Subsequently, micro-computed tomography and histological assays were used to evaluate the effect of alpha-mangostin in preventing inflammatory osteolysis. Results: We found that alpha-mangostin could inhibit RANKL-induced osteoclastogenesis and reduced osteoclast-related gene expression in vitro. F-actin ring immunofluorescence and resorption pit assays indicated that alpha-mangostin also inhibited osteoclast functions. It achieved these effects by disrupting the activation of NF-kappa B/mitogen-activated protein kinase signaling pathways. Our in vivo data revealed that alpha-mangostin could protect mouse calvarial bone from osteolysis. Conclusions: Our findings demonstrate that alpha-mangostin can inhibit osteoclastogenesis both in vitro and in vivo and may be a potential option for treating osteoclast-related diseases.