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The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury (ALI), recently implicated in COVID-19-induced bone loss. This study examined the effects of LPS-induced ALI on bone phenotype and explored the role of 2-N, 6-O sulfated chitosan (26SCS) in mitigating pneumonia-induced bone loss via inflammatory response modulation. Our findings show that 26SCS effectively reaches bone tissue after oral administration. It promotes macrophage polarization to the M2 phenotype, alleviating immune cascade reactions and inhibiting osteoclast-mediated bone resorption. Increased M2 macrophages support type H vessel formation, enhancing inflammatory bone vascularization. These effects foster a favorable osteogenic microenvironment and mitigate ALI-induced bone loss. While dexamethasone is effective in reducing inflammation, it can aggravate ALI-induced bone loss. Our research offers a therapeutic strategy targeting the lung-bone axis for inflammation-induced bone loss.<\/jats:p>","DOI":"10.1038\/s41413-025-00475-4","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:39:53Z","timestamp":1770287993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sulfated chitosan mitigates acute lung injury induced bone loss via immunoregulation"],"prefix":"10.1038","volume":"14","author":[{"given":"Yongxian","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luli","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuwei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaze","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyuan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0509-7334","authenticated-orcid":false,"given":"Changsheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"475_CR1","doi-asserted-by":"crossref","unstructured":"Cheng, L. et al. 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