Amlexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss

摘要: The activity of protein kinases IKK-e and TANK-binding kinase 1 (TBK1) has been shown to be associated with inflammatory diseases. As an inhibitor TBK1, amlexanox is anti-inflammatory, anti-allergic, immunomodulator used for treatment ulcer, allergic rhinitis asthma in clinic. We hypothesized that may osteoclast-related diseases which frequently a low grade systemic inflammation. In this study, we investigated the effects on RANKL-induced osteoclastogenesis vitro ovariectomy-mediated bone loss vivo. primary marrow derived macrophages (BMMs), inhibited osteoclast formation resorption. At molecular level, suppressed activation nuclear factor-κB (NF-κB), mitogen-activated (MAPKs), c-Fos NFATc1. Amlexanox decreased expression osteoclast-specific genes, including TRAP, MMP9, Cathepsin K Moreover, enhanced osteoblast differentiation BMSCs. ovariectomized (OVX) mouse model, prevented OVX-induced by suppressing activity. Taken together, our results demonstrate suppresses prevents loss. Therefore, considered as new therapeutic candidate diseases, such osteoporosis rheumatoid arthritis.