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However, its specific role in synovial macrophages, the key immune cells of OA related tissues, remains entirely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Herein, the RhoA expression in human and mouse OA synovium was analyzed. A macrophage-specific RhoA conditional knockout (cKO) mouse model was generated. Histological staining, OARSI scoring, and micro-CT were used to assess cartilage damage, while Western blot, immunofluorescence staining, and ELISA assessed changes in cellular function. Transcriptome sequencing and validation of signaling pathways were conducted using tissues and cells from patients with OA and OA mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The collected results indicate that\u00a0RhoA expression was significantly upregulated in synovial macrophages from OA patients and mice, correlating with disease severity. Contrary to its reported role in chondrocytes or endothelial cells, macrophage-specific RhoA deletion exacerbated OA, demonstrating enhanced cartilage destruction, subchondral bone loss, and synovitis. RhoA-deficient macrophages exhibited a pro-inflammatory M1 polarization and secreted high levels of IL-17C. This cytokine was necessary and sufficient to induce chondrocyte senescence, as evidenced by increased p53\/p21, ROS, mitochondrial dysfunction, and suppressed autophagy, via activation of the PI3K\/AKT\/mTOR pathway. Mechanistically, RhoA ablation in macrophages activated the Hippo pathway effectors YAP\/CCN2, leading to IL-17C transcription, independently of the canonical ROCK pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, present study reveals a previously unrecognized, protective role for macrophage RhoA in OA. It functions as a critical brake on a novel YAP-IL-17C axis, thereby preserving chondrocyte. This study redefines RhoA's role in joint homeostasis and nominates IL-17C as a potential therapeutic target for OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s10565-026-10151-w","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T16:06:16Z","timestamp":1769875576000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synovial macrophage rhoa protects against osteoarthritis by suppressing YAP\/IL-17C mediated chondrocyte senescence"],"prefix":"10.1007","volume":"42","author":[{"given":"Yizhou","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9347-0310","authenticated-orcid":false,"given":"Gang","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7885-2903","authenticated-orcid":false,"given":"Jiasong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3055-3063","authenticated-orcid":false,"given":"Lixin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"10151_CR1","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1002\/art.22337","volume":"56","author":"AB Blom","year":"2007","unstructured":"Blom AB, van Lent PL, Libregts S, Holthuysen AE, van der Kraan PM, van Rooijen N, et al. 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Cell Biosci. 2021;11:210. https:\/\/doi.org\/10.1186\/s13578-021-00725-y.","journal-title":"Cell Biosci"}],"container-title":["Cell Biology and Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10565-026-10151-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10565-026-10151-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10565-026-10151-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T01:27:54Z","timestamp":1770859674000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10565-026-10151-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,31]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["10151"],"URL":"https:\/\/doi.org\/10.1007\/s10565-026-10151-w","relation":{},"ISSN":["1573-6822"],"issn-type":[{"value":"1573-6822","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,31]]},"assertion":[{"value":"13 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The observational study involving clinical samples in this study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and was approved by the Ethics Committee of Ganzhou Hospital (Approval number: TY-ZKY2024-141\u201301, date: 10\/20\/2024). All procedures involving human samples were designed to respect the rights, dignity, and privacy of participants. Informed consent was obtained from all participants, or their legally authorized representatives. The specimens collected in this study were from tissues that had to be removed during surgery for therapeutic needs, so that participants did not have potential risks and burdens.All animal use in this study was approved by the Ethics Committee of Southern Medical University (Approval number: SMU-L2018158, date: 10\/1\/2018). All of the experiments were performed in accordance with the Basel Declaration.","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 to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical trial number"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"30"}}