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CS treatment or ROR\u03b1 overexpression attenuates osteoclastogenesis in a collagen\u2010induced arthritis mouse model. However, the mechanism by which CS and ROR\u03b1 regulate osteoclast differentiation remains largely unknown. Thus, we aimed to investigate the role of CS and ROR\u03b1 in osteoclastogenesis and their underlying mechanism. CS inhibited osteoclast differentiation, but ROR\u03b1 deficiency did not affect osteoclast differentiation and CS\u2010mediated inhibition of osteoclastogenesis. CS enhanced adenosine monophosphate\u2010activated protein kinase (AMPK) phosphorylation and sirtuin1 (Sirt1) activity, leading to nuclear factor\u2010\u03baB (NF\u2010\u03baB) inhibition by decreasing acetylation at Lys310 of p65. The NF\u2010\u03baB inhibition was restored by AMPK inhibitor, but the effects of CS on AMPK and NF\u2010\u03baB were not altered by ROR\u03b1 deficiency. CS also induced osteoclast apoptosis, which may be due to sustained AMPK activation and consequent NF\u2010\u03baB inhibition, and the effects of CS were significantly reversed by interleukin\u20101\u03b2 treatment. Collectively, these results indicate that CS inhibits osteoclast differentiation and survival by suppressing NF\u2010\u03baB via the AMPK\u2013Sirt1 axis in a ROR\u03b1\u2010independent manner. Furthermore, CS protects against bone destruction in lipopolysaccharide\u2010 and ovariectomy\u2010mediated bone loss mouse models, suggesting that CS is a useful therapeutic candidate for treating inflammation\u2010induced bone diseases and postmenopausal osteoporosis.<\/jats:p>","DOI":"10.1002\/jcp.31064","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T10:09:52Z","timestamp":1687169392000},"page":"2063-2075","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Cholesterol sulfate inhibits osteoclast differentiation and survival by regulating the AMPK\u2013Sirt1\u2013NF\u2010\u03baB pathway"],"prefix":"10.1002","volume":"238","author":[{"given":"Jin Ha","family":"Park","sequence":"first","affiliation":[{"name":"Department of Life Science and the Research Center for Cellular Homeostasis Ewha Womans University Seoul 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