{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:08:55Z","timestamp":1784768935082,"version":"3.55.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T00:00:00Z","timestamp":1735948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170934"],"award-info":[{"award-number":["82170934"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870743"],"award-info":[{"award-number":["81870743"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sichuan Science and Technology Program","award":["2024YFFK0201"],"award-info":[{"award-number":["2024YFFK0201"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The function and mechanism of pri-miRNA N6-methyladenosine (m6A) modification in promoting miRNA maturation and regulating osteoblastic differentiation are not fully understood. The aim of this study was to investigate the role and regulatory mechanism of miRNA shear maturation regulated by methyltransferase like 3 (METTL3) in human adipose-derived stem cell (hASC) osteogenesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>First, we found METTL3 promoted osteogenesis both in vivo and in vitro. Subsequently, 3 pri-miRNAs with the most significant methylated peaks were identified through methylated RNA immunoprecipitation sequencing. Through quantitative real-time polymerase chain reaction, MeRIP-qPCR, and co-immunoprecipitation, it was determined that METTL3 promoted the processing of hsa-miR-4526 by mediating pri-miR4526\/5190 m6A modification. Subsequent in vivo and in vitro experiments demonstrated that hsa-miR-4526 promoted osteogenesis. Dual luciferase reporter assay was performed to verify that hsa-miR-4526 regulated osteogenic differentiation through TUBB3. It was found that TUBB3 can inhibit hASC osteogenesis. Further rescue experiments confirmed that METTL3 inhibited TUBB3 expression through hsa-miR-4526, thereby regulating osteogenic differentiation. RNA-seq revealed that TUBB3 may be involved in cell metabolism, calcium enrichment, osteoclast differentiation, and other pathways.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study is the first to investigate the mechanism of pri-miRNA m6A modification in regulating hASC osteogenesis, presenting a novel idea and method for repairing bone defects.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/stmcls\/sxae089","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T02:56:21Z","timestamp":1736132181000},"source":"Crossref","is-referenced-by-count":6,"title":["METTL3 promotes osteogenesis by regulating N6-methyladenosine-dependent primary processing of hsa-miR-4526"],"prefix":"10.1093","volume":"43","author":[{"given":"Yidan","family":"Song","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology,\u00a0National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University , Chengdu 610041, Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology,\u00a0National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University , Chengdu 610041, Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihua","family":"Pan","sequence":"additional","affiliation":[{"name":"The First People\u2019s Hospital of Longquanyi District, West China Longquan Hospital Sichuan University , Chengdu 610199, Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Gu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology,\u00a0National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University , Chengdu 610041, Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentian","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology,\u00a0National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University , Chengdu 610041, Sichuan 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