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However, the contribution of m\n                    <jats:sup>6<\/jats:sup>\n                    A-dependent regulation of circular RNAs (circRNAs) to chondrocyte senescence and OA progression remains poorly understood. We aimed to elucidate whether m\n                    <jats:sup>6<\/jats:sup>\n                    A-mediated control of circRNAs regulates chondrocyte senescence and to define the underlying molecular mechanisms contributing to OA progression. Here, we identified an OA-associated circRNA, circHIPK2, and demonstrated that its abundance and function are regulated by an m\n                    <jats:sup>6<\/jats:sup>\n                    A reader\u2013dependent decay mechanism. circHIPK2 expression was reduced in human OA cartilage, and its depletion exacerbated chondrocyte senescence, increased senescence-associated secretory phenotype (SASP) gene expression, and impaired autophagy both in vitro and in the destabilization of the medial meniscus (DMM) model. Mechanistically, YTH N\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine RNA-binding protein 2 (YTHDF2) recognized m\n                    <jats:sup>6<\/jats:sup>\n                    A-modified circHIPK2 and facilitated its degradation, thereby reducing circHIPK2 stability. Functionally, circHIPK2 directly interacted with RAB22A. Loss of circHIPK2 weakened this interaction, enhanced RAB22A\u2013PI3K association, activated the PI3K\u2013AKT\u2013mTOR signaling pathway, disrupted autophagic flux, and accelerated senescence-associated phenotypes. Notably, the protective effects of circHIPK2 were abolished in RAB22A-binding\u2013deficient circHIPK2 mutants, establishing a direct link between molecular interaction and functional outcome. Furthermore, we encapsulated circHIPK2 into lipid nanoparticles (circHIPK2-LNP) for transient intra-articular delivery. Intra-articular administration of circHIPK2-LNP attenuated chondrocyte senescence and alleviated OA progression in DMM mice. Collectively, m\n                    <jats:sup>6<\/jats:sup>\n                    A-dependent YTHDF2-mediated degradation of circHIPK2 promotes chondrocyte senescence and OA progression by disrupting autophagy, identifying circHIPK2 as a potential therapeutic target and prognostic biomarker for cartilage aging in OA.\n                  <\/jats:p>","DOI":"10.1186\/s43556-026-00441-4","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T07:44:46Z","timestamp":1774597486000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["YTH N6-methyladenosine RNA binding protein 2 mediated m6A modification of circHIPK2 promotes cellular senescence and osteoarthritis progression by inhibiting autophagy"],"prefix":"10.1186","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0640-9056","authenticated-orcid":false,"given":"Dianbo","family":"Long","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhencan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiwen","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zengfa","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongrui","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanlin","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aishan","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiyang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4978-4136","authenticated-orcid":false,"given":"Guping","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1253-0610","authenticated-orcid":false,"given":"Yan","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"441_CR1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1056\/NEJMcp1903768","volume":"384","author":"L Sharma","year":"2021","unstructured":"Sharma L. 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