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In this study, \u03b3-irradiation-killed <jats:italic>S. aureus<\/jats:italic> (IKSA) was applied to simulate the inflammation and explore the mechanism of systemic bone loss caused by it. In this study, we found that the systemic application of IKSA caused bone loss in mice through increasing osteoclasts and decreasing osteoblasts. An immune response profile with up-regulated COX-2 is identified based on our transcriptional data from IKSA mice bone marrow cells. COX-2 expression is widely up-regulated in bone marrow immune cells, such as myeloid-derived suppressor cells (MDSCs), neutrophils and macrophages in the IKSA-treated mice. Mechanistically, COX-2 stimulated the increasing proportion of MDSCs and neutrophils and the inflammatory response of the bone marrow immune cells, that may regulate bone metabolism. Importantly, COX-2 inhibitor, celecoxib could rescue the bone loss induced by IKSA, which may reason from decrease of inflammatory gene expression in MDSCs, neutrophils and macrophages. Excitingly, COX-2 expression is also increased in bone marrow from mice and patients with <jats:italic>S. aureus<\/jats:italic> osteomyelitis. These findings suggested a therapeutic potential for inhibiting COX-2 in combating bone loss in <jats:italic>S. aureus<\/jats:italic> osteomyelitis.<\/jats:p>","DOI":"10.1186\/s10020-025-01202-9","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T09:30:21Z","timestamp":1746610221000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["COX-2 inhibition as a therapeutic strategy for bone loss in Staphylococcus aureus osteomyelitis"],"prefix":"10.1186","volume":"31","author":[{"given":"Yuhui","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jishan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiqun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"issue":"1","key":"1202_CR1","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1186\/s13643-021-01690-w","volume":"10","author":"H Al-Waeli","year":"2021","unstructured":"Al-Waeli H, Reboucas AP, Mansour A, Morris M, Tamimi F, Nicolau B. 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Each participant in this research provided informed consent before taking part. (Approval Number: NFEC-2020-074). All procedures involving animals received approval from the Institutional Animal Care and Use Committee of Nanfang Hospital and were conducted according to the guidelines of the National Regulations on the Management of Laboratory Animals. (Approval Number: NFYY-2022-01037).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"177"}}