{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:34:39Z","timestamp":1784302479802,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ9445"],"award-info":[{"award-number":["2024JJ9445"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) pathogenesis involves dysregulated macrophage polarisation, yet the epigenetic mechanisms governing this process remain poorly understood. This study investigates how METTL3 promotes pri\u2010miR\u2010221 maturation via m6A modification to regulate macrophage M1\/M2 polarisation and immune inflammation in RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>METTL3 mRNA levels in serum from RA patients and healthy controls were detected by RT\u2010qPCR and their correlations with C\u2010reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were analysed. Peripheral blood mononuclear cells (PBMCs) were isolated, differentiated into macrophages and assessed for METTL3 expression using RT\u2010qPCR and Western blot. M1\/M2 polarisation was evaluated via marker genes (iNOS, Arg\u20101) and released cytokines (IL\u20106, TNF\u2010\u03b1 for M1; TGF\u2010\u03b21, IL\u201010 for M2) using Western blot and ELISA, and verified by immunofluorescence (CD68+\/CD86+ for M1; CD68+\/CD206+ for M2). Methylated RNA immunoprecipitation and RNA stability assays were used to identify METTL3\u2010mediated m6A modification of pri\u2010miR\u2010221, while RNA immunoprecipitation was conducted to confirm YTHDF1\/2\/3\u2010pri\u2010miR\u2010221 interactions. In\u00a0vivo, a rat RA model was established, with METTL3 expression and ankle pathology analysed via immunohistochemistry, haematoxylin\u2013eosin and Safranin O\u2010fast green staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>METTL3 was significantly upregulated in RA serum, isolated PBMCs and derived macrophages, positively correlating with CRP and ESR. METTL3 knockdown in macrophages reduced M1 markers and increased M2 markers, indicating METTL3 knockdown promoted M2 polarisation and inhibited M1 polarisation. METTL3 stabilised pri\u2010miR\u2010221 via m6A, and pri\u2010miR\u2010221 overexpression reversed the effect of METTL3 knockdown on M2 polarisation. In RA rats, METTL3 was elevated, exacerbating ankle joint destruction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>METTL3 knockdown suppresses m6A\u2010dependent pri\u2010miR\u2010221 maturation, rebalancing macrophage polarisation and attenuating ankle joint destruction in RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1440-1681.70099","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T06:42:11Z","timestamp":1766385731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>METTL3<\/scp>\n                    \u2010Mediated\n                    <scp>m6A<\/scp>\n                    Modification Facilitates pri\u2010\n                    <scp>miR<\/scp>\n                    \u2010221 Maturation to Regulate Macrophage\n                    <scp>M1<\/scp>\n                    \/\n                    <scp>M2<\/scp>\n                    Polarisation and Immune Inflammation in Rheumatoid Arthritis"],"prefix":"10.1111","volume":"53","author":[{"given":"Xiangping","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Geriatric The Second Affiliated Hospital of Hunan University of Chinese Medicine  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1613-3526","authenticated-orcid":false,"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"The Fourth Department of Orthopedics The Second Affiliated Hospital of Hunan University of Chinese Medicine  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Wu","sequence":"additional","affiliation":[{"name":"The Fourth Department of Orthopedics The Second Affiliated Hospital of Hunan University of Chinese Medicine  Changsha 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