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Such coordination is partly governed by ribonucleic acid (RNA) epigenetic mechanisms, however, the role of the predominant RNA modification N\n                    <jats:sup>6<\/jats:sup>\n                    \u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) in this process remains unclear. Herein, we identify an epigenetic\u2013metabolic pathway in which Wilms' Tumor 1\u2010Associating Protein (WTAP)\u2010mediated m\n                    <jats:sup>6<\/jats:sup>\n                    A modification stabilizes low\u2010density lipoprotein receptor\u2010related protein 1 (LRP1) and redirects lipid metabolism toward chondrogenesis. Loss\u2010of\u2010function assays demonstrate that WTAP is required for the chondrogenic differentiation of BMSCs, as its depletion suppresses the expression of multiple cartilage\u2010associated genes. Mechanistically, WTAP enhances m\n                    <jats:sup>6<\/jats:sup>\n                    A methylation and stabilizes\n                    <jats:italic>Lrp1<\/jats:italic>\n                    transcripts, a key regulator of cholesterol metabolism and matrix synthesis, thereby driving lipid metabolic reprogramming toward chondrogenesis. Structure\u2010based screening identified silibinin and estradiol benzoate as LRP1\u2010specific agonists that activate the WTAP\u2013LRP1 pathway to promote cartilage repair in vivo. Collectively, our findings establish m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010dependent metabolic reprogramming as a pivotal epigenetic mechanism of cartilage regeneration with therapeutic potential for promoting chondrogenesis.\n                  <\/jats:p>","DOI":"10.1002\/advs.75479","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T10:52:57Z","timestamp":1778064777000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["WTAP\u2010Mediated m\n                    <sup>6<\/sup>\n                    A Modification Targets the LRP1\u2010Lipid Metabolism Axis to Regulate Joint Cartilage Regeneration"],"prefix":"10.1002","volume":"13","author":[{"given":"Chenyan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Geriatric Dentistry NMPA Key Laboratory for Dental Materials Peking University School and Hospital of Stomatology &amp; National Center of Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices  Beijing P. R. China"},{"name":"Peking University Hospital of Stomatology Sanya Division (Sanya Stomatology Center) Sanya  Hainan P. R. China"},{"name":"Nanjing Stomatological Hospital Affiliated Hospital of Medical School Institute of Stomatology Nanjing University Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Cranial\u2010Facial Growth and Development Center Peking University School and Hospital of Stomatology  Beijing P. R. 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