Beta-Boswellic Acid Inhibits Rankl-Induced Osteoclast Differentiation And Function By Attenuating Nf-Kappa B And Btk-Plc Gamma 2 Signaling Pathways

Osteoporosis is a systemic metabolic bone disorder that is caused by an imbalance in the functions of osteoclasts and osteoblasts and is characterized by excessive bone resorption by osteoclasts. Targeting osteoclast differentiation and bone resorption is considered a good fundamental solution for overcoming bone diseases. beta-boswellic acid (beta BA) is a natural compound found in Boswellia serrata, which is an active ingredient with anti-inflammatory, anti-rheumatic, and anti-cancer effects. Here, we explored the anti-resorptive effect of beta BA on osteoclastogenesis. beta BA significantly inhibited the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by receptor activator of nuclear factor-B ligand (RANKL) and suppressed bone resorption without any cytotoxicity. Interestingly, beta BA significantly inhibited the phosphorylation of I kappa B, Btk, and PLC gamma 2 and the degradation of I kappa B. Additionally, beta BA strongly inhibited the mRNA and protein expression of c-Fos and NFATc1 induced by RANKL and subsequently attenuated the expression of osteoclast marker genes, such as OC-STAMP, DC-STAMP, beta 3-integrin, MMP9, ATP6v0d2, and CtsK. These results suggest that beta BA is a potential therapeutic candidate for the treatment of excessive osteoclast-induced bone diseases such as osteoporosis.