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An excessive immune inflammatory response causes excessive activation of osteoclasts, leading to bone loss and bone destruction. The signaling protein stimulator of interferon gene (STING) can regulate the immune response of osteoclasts. C\u2010176 is a furan derivative that can inhibit activation of the STING pathway and exert anti\u2010inflammatory effects. The effect of C\u2010176 on osteoclast differentiation is not yet clear. In this study, we found that C\u2010176 could inhibit STING activation in osteoclast precursor cells and inhibit osteoclast activation induced by nuclear factor \u03baB ligand receptor activator in a dose\u2010dependent manner. After treatment with C\u2010176, the expression of the osteoclast differentiation marker genes nuclear factor of activated T\u2010cells c1(NFATc1), cathepsin K, calcitonin receptor, and V\u2010ATPase a3 decreased. In addition, C\u2010176 reduced actin loop formation and bone resorption capacity. The WB results showed that C\u2010176 downregulated the expression of the osteoclast marker protein NFATc1 and inhibited activation of the STING\u2010mediated NF\u2010\u03baB pathway. We also found that C\u2010176 could inhibit the phosphorylation of mitogen\u2010activated protein kinase signaling pathway factors induced by RANKL. Moreover, we verified that C\u2010176 could reduce LPS\u2010induced bone absorption in mice, reduce joint destruction in knee arthritis induced by meniscal instability, and protect against cartilage matrix loss in ankle arthritis induced by collagen immunity. In summary, our findings demonstrated that C\u2010176 could inhibit the formation and activation of osteoclasts and could be used as a potential therapeutic agent for inflammatory osteolytic diseases.<\/jats:p>","DOI":"10.1096\/fj.202201600r","type":"journal-article","created":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T20:00:00Z","timestamp":1678564800000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["The\n                    <scp>STING<\/scp>\n                    inhibitor C\u2010176 attenuates osteoclast\u2010related osteolytic diseases by inhibiting osteoclast differentiation"],"prefix":"10.1096","volume":"37","author":[{"given":"Zhen\u2010cheng","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 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