{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:24:26Z","timestamp":1787199866922,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072408"],"award-info":[{"award-number":["82072408"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    N\n                    <jats:sup>6<\/jats:sup>\n                    \u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) plays a critical role in osteoarthritis (OA) pathogenesis. This study investigates the role of the m\n                    <jats:sup>6<\/jats:sup>\n                    A reader insulin\u2010like growth factor 2 mRNA\u2010binding protein 3 (IGF2BP3) in OA progression. OA models were established in\u00a0vivo through destabilization of the medial meniscus (DMM) surgery in mice and in\u00a0vitro by stimulating primary chondrocytes with interleukin\u20101\u03b2 (IL\u20101\u03b2). Cartilage destruction was assessed histopathologically. Chondrocyte viability, proliferation, and apoptosis were measured by CCK\u20108, EdU, and flow cytometry, respectively. Inflammatory cytokine levels, lactate, glucose, and total m\n                    <jats:sup>6<\/jats:sup>\n                    A were quantified using commercial kits. Expression levels of IGF2BP3, extracellular matrix protein 1 (ECM1), ECM turnover markers, and glycolysis\u2010related genes were analyzed by RT\u2010qPCR, Western blot, immunohistochemistry, and immunofluorescence. Potential m\n                    <jats:sup>6<\/jats:sup>\n                    A modification sites in ECM1 transcripts were predicted using the SRAMP database, and IGF2BP3\u2010mediated, m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010dependent regulation of ECM1 was validated through RNA immunoprecipitation (RIP), MeRIP\u2010qPCR, and actinomycin D decay assays. Results revealed elevated levels of IGF2BP3, ECM1, m\n                    <jats:sup>6<\/jats:sup>\n                    A modification, and glycolytic activity in OA cartilage and IL\u20101\u03b2\u2010treated chondrocytes. IGF2BP3 knockdown reversed IL\u20101\u03b2\u2010induced reductions in chondrocyte viability and proliferation, suppressed apoptosis, decreased inflammatory cytokine secretion, attenuated ECM degradation, and reduced glycolytic flux in\u00a0vitro, while also mitigating cartilage damage and matrix breakdown in\u00a0vivo. Mechanistically, IGF2BP3 stabilized ECM1 mRNA in an m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010dependent manner, thereby modulating ECM1 expression. Restoration of ECM1 expression abolished the chondroprotective effects of IGF2BP3 knockdown against injury, inflammation, and enhanced glycolysis. In conclusion, IGF2BP3 enhances ECM1 expression via an m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010dependent pathway, thereby promoting glycolysis and exacerbating OA progression.\n                  <\/jats:p>","DOI":"10.1002\/kjm2.70280","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T03:53:19Z","timestamp":1787197999000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>IGF2BP3<\/scp>\n                    Overexpression Accelerates Osteoarthritis Progression by Promoting Glycolysis via\n                    <scp>\n                      m\n                      <sup>6<\/sup>\n                      A\n                    <\/scp>\n                    \u2010Dependent Stabilization of\n                    <scp>ECM1 mRNA<\/scp>"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7772-7270","authenticated-orcid":false,"given":"Xing\u2010Shi","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Xiang","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng\u2010Liang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi\u2010Fu","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1902-0199","authenticated-orcid":false,"given":"Ke\u2010Rong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"16072","DOI":"10.1038\/nrdp.2016.72","article-title":"Osteoarthritis","volume":"2","author":"Martel\u2010Pelletier J.","year":"2016","journal-title":"Nature Reviews. 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Molecular Cell Biology"},{"issue":"16","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","DOI":"10.1111\/jcmm.70019","article-title":"Gubi Decoction Mitigates Knee Osteoarthritis via Promoting Chondrocyte Autophagy Through METTL3\u2010Mediated ATG7 m6A Methylation","volume":"28","author":"Cui L.","year":"2024","journal-title":"Journal of Cellular and Molecular Medicine"},{"issue":"1","key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s12276-023-01135-5","article-title":"WTAP\u2010Mediated m6A Modification of FRZB Triggers the Inflammatory Response via the Wnt Signaling Pathway in Osteoarthritis","volume":"56","author":"An X.","year":"2024","journal-title":"Experimental & Molecular Medicine"},{"issue":"1","key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s12943-023-01841-8","article-title":"m6A\u2010Regulated Tumor Glycolysis: New Advances in Epigenetics and Metabolism","volume":"22","author":"Yue S. 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Y.","year":"2023","journal-title":"Biomarker Research"},{"issue":"46","key":"e_1_2_9_16_1","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202401399","article-title":"Lactylation\u2010Driven IGF2BP3\u2010Mediated Serine Metabolism Reprogramming and RNA m6A\u2010Modification Promotes Lenvatinib Resistance in HCC","volume":"11","author":"Lu Y.","year":"2024","journal-title":"Advanced Science"},{"issue":"1","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41413-025-00434-z","article-title":"IGF2BP3\u2010Mediated m6A Modification of RASGRF1 Promoting Joint Injury in Rheumatoid Arthritis","volume":"13","author":"Geng Q.","year":"2025","journal-title":"Bone Research"},{"issue":"14","key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"5731","DOI":"10.7150\/ijbs.99738","article-title":"Mechanistic Study of Celastrol\u2010Mediated Inhibition of Proinflammatory Activation of Macrophages in IgA Nephropathy via Down\u2010Regulating ECM1","volume":"20","author":"Zhao J.","year":"2024","journal-title":"International Journal of Biological Sciences"},{"issue":"3","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1136\/gutjnl-2024-333213","article-title":"ECM1 Attenuates Hepatic Fibrosis by Interfering With Mediators of Latent TGF\u2010\u03b21 Activation","volume":"74","author":"Link F.","year":"2025","journal-title":"Gut"},{"issue":"2","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/ni.1983","article-title":"ECM1 Controls T(H)2 Cell Egress From Lymph Nodes Through Re\u2010Expression of S1P(1)","volume":"12","author":"Li Z.","year":"2011","journal-title":"Nature Immunology"},{"issue":"6","key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1073\/pnas.1912774117","article-title":"ECM1 Is an Essential Factor for the Determination of M1 Macrophage Polarization in IBD in Response to LPS Stimulation","volume":"117","author":"Zhang Y.","year":"2020","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"8","key":"e_1_2_9_22_1","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1096\/fj.201600261R","article-title":"Extracellular Matrix Protein 1, a Direct Targeting Molecule of Parathyroid Hormone\u2010Related Peptide, Negatively Regulates Chondrogenesis and Endochondral Ossification via Associating With Progranulin Growth Factor","volume":"30","author":"Kong L.","year":"2016","journal-title":"FASEB Journal"},{"issue":"1","key":"e_1_2_9_23_1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1186\/s13018-024-05034-x","article-title":"Identification of Novel Drug Targets for Osteoarthritis by Integrating Genetics and Proteomes From Blood","volume":"19","author":"Song S.","year":"2024","journal-title":"Journal of Orthopaedic Surgery and Research"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2023.111291","article-title":"Downregulation of Extracellular Matrix Protein 1 Effectively Ameliorates Osteoarthritis Progression in Vivo","volume":"126","author":"Feng D.","year":"2024","journal-title":"International Immunopharmacology"},{"key":"e_1_2_9_25_1","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.2147\/DDDT.S210220","article-title":"Aucubin Protects Chondrocytes Against IL\u20101\u03b2\u2010Induced Apoptosis in Vitro and Inhibits Osteoarthritis in Mice Model","volume":"13","author":"Wang B. W.","year":"2019","journal-title":"Drug Design, Development and Therapy"},{"issue":"1","key":"e_1_2_9_26_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","article-title":"Osteoarthritis Cartilage Histopathology: Grading and Staging","volume":"14","author":"Pritzker K. 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Modification","volume":"31","author":"Di Timoteo G.","year":"2020","journal-title":"Cell Reports"},{"issue":"1","key":"e_1_2_9_30_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13075-023-03035-5","article-title":"FTO\u2010Mediated m6A Demethylation of Pri\u2010miR\u20103591 Alleviates Osteoarthritis Progression","volume":"25","author":"Liu W.","year":"2023","journal-title":"Arthritis Research & Therapy"},{"issue":"1","key":"e_1_2_9_31_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s12964-023-01228-8","article-title":"N6\u2010Methyladenosine (m6A) Methyltransferase WTAP\u2010Mediated miR\u201092b\u20105p Accelerates Osteoarthritis Progression","volume":"21","author":"Lin Z.","year":"2023","journal-title":"Cell Communication and Signaling: CCS"},{"issue":"5","key":"e_1_2_9_32_1","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1007\/s11010-024-05170-2","article-title":"FOXM1\u2010Activated IGF2BP3 Promotes Cell Malignant Phenotypes and M2 Macrophage Polarization in Hepatocellular Carcinoma by Inhibiting Ferroptosis via Stabilizing RRM2 mRNA in an m6A\u2010Dependent Manner","volume":"480","author":"Gao H.","year":"2025","journal-title":"Molecular and Cellular Biochemistry"},{"issue":"1","key":"e_1_2_9_33_1","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1186\/s12951-024-02932-4","article-title":"m6A\u2010Modified Exosome\u2010Derived circHIF1\u03b1 Binding to KH Domain of IGF2BP3 Mediates DNA Damage and Arrests G1\/S Transition Phase to Resists Bacterial Infection in Bacteremia","volume":"22","author":"Yu J.","year":"2024","journal-title":"Journal of Nanobiotechnology"},{"key":"e_1_2_9_34_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhazmat.2024.135093","article-title":"m6A\u2010Mediated HDAC9 Upregulation Promotes Particulate Matter\u2010Induced Airway Inflammation via Epigenetic Control of DUSP9\u2010MAPK Axis and Acts as an Inhaled Nanotherapeutic Target","volume":"477","author":"Zeng Y.","year":"2024","journal-title":"Journal of Hazardous Materials"},{"issue":"6","key":"e_1_2_9_35_1","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1016\/j.jaci.2021.11.024","article-title":"Hsa_circ_0004287 Inhibits Macrophage\u2010Mediated Inflammation in an N6\u2010Methyladenosine\u2010Dependent Manner in Atopic Dermatitis and Psoriasis","volume":"149","author":"Yang L.","year":"2022","journal-title":"Journal of Allergy and Clinical Immunology"},{"issue":"1","key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1186\/s12967-023-04173-9","article-title":"Expression Pattern Analysis of m6A Regulators Reveals IGF2BP3 as a Key Modulator in Osteoarthritis Synovial Macrophages","volume":"21","author":"Lu Y.","year":"2023","journal-title":"Journal of Translational Medicine"},{"key":"e_1_2_9_37_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1327852","article-title":"Glycolysis: An Emerging Regulator of 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