Being the principal cells responsible for bone resorption and pathologic bone loss, osteoclasts have become the main target for antiresorptive treatment. Cumambrin A is a natural compound isolated from Chrysanthemum indicum L. and belongs to a member of the sesquiterpene lactone family. To date, the therapeutic effect of cumambrin A on osteoporosis and its mechanisms of action are not known. In this study, we found that cumambrin A can significantly inhibit osteoclast formation and bone resorption through the suppression of receptor activator of NF-κB ligand (RANKL)-induced NF-κB and nuclear factor of activated T-cell activity and ERK phosphorylation. Furthermore, cumambrin A inhibits the expression of osteoclast marker genes including cathepsin K, calcitonin receptor, and V-ATPase d2. Using an in vivo ovariectomized mouse model, we showed that cumambrin A protects against estrogen withdrawal-induced bone loss. Collectively, our results reveal that cumambrin A can suppress osteoclast formation, bone resorption, and RANKL-induced signaling pathways, suggesting that cumambrin A is a potential therapeutic agent for the treatment of osteoporosis.-Zhou, L., Liu, Q., Hong, G., Song, F., Zhao, J., Yuan, J., Xu, J., Tan, R. X., Tickner, J., Gu, Q., Xu, J. Cumambrin A prevents OVX-induced osteoporosis via the inhibition of osteoclastogenesis, bone resorption, and RANKL signaling pathways.
Keywords: ERK; NF-κB; NFATc1; osteolysis.