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Osteoclasts (OCs) are critical players in the process. Concerns regarding the long\u2010term efficacy and side effects of current frontline therapies, however, remain. Alternative therapies are still required. The aim of this work was to investigate the involvement of Tenacissoside H (TDH) in RANKL\u2010mediated OC differentiation, as well as inflammatory osteolysis and associated processes. In vitro, bone marrow\u2010derived macrophages (BMMs) cultured with RANKL and M\u2010CSF were used to detect TDH in the differentiation and function of OCs. Real\u2010time quantitative PCR was used to measure the expression of specific genes and inflammatory factors in OCs. Western blot was used to identify NFATc1, IKK, NF\u2010\u03baB, MAPK pathway, and oxidative stress\u2010related components. Finally, an LPS\u2010mediated calvarial osteolysis mouse model was employed to explore TDH's role in inflammatory osteolysis. The results showed that in vivo TDH inhibited the differentiation and resorption functions of OCs and down\u2010regulated the transcription of osteoclast\u2010specific genes, as well as <jats:italic>Il\u20101\u03b2<\/jats:italic>, <jats:italic>Il\u20106<\/jats:italic> and <jats:italic>Tnf\u2010\u03b1<\/jats:italic>. In addition, TDH inhibited the IKK and NF\u2010\u03baB signalling pathways and down\u2010regulated the level of ROS. In vivo studies revealed that TDH improves the bone loss caused by LPS. TDH may be a new candidate or treatment for osteoclast\u2010associated inflammatory osteolytic disease.<\/jats:p>","DOI":"10.1111\/cpr.13535","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T10:30:33Z","timestamp":1691490633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["IKK\/NF\u2010\u03baB and ROS signal axes are involved in Tenacissoside H mediated inhibitory effects on LPS\u2010induced inflammatory osteolysis"],"prefix":"10.1111","volume":"57","author":[{"given":"Xiaoxiao","family":"Xie","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Regenerative Medicine, Orthopaedic Department The First Affiliated Hospital of Guangxi Medical University  Nanning Guangxi China"},{"name":"Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co\u2010constructed by the Province and Ministry, Life Sciences 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