{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:59:39Z","timestamp":1790765979503,"version":"4.1.0"},"reference-count":165,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004761","name":"Natural Science Foundation of Hainan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017695","name":"Health Commission of Hunan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017695","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Intervertebral disc degeneration (IDD) is the fundamental pathological process underlying low back pain, a major cause leading to disability worldwide. As the most prevalent methylation modification in eukaryotic RNA molecules, N6-methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) is involved in various diseases and cellular processes by regulating RNA fate. Methyltransferase-like protein 3 (METTL3) is the sole catalytic component of the methyltransferase complex and mediates m\n                    <jats:sup>6<\/jats:sup>\n                    A deposition on target RNAs. METTL3 is ubiquitously expressed and modulated by a variety of factors at the transcriptional and post-transcriptional levels. METTL3 expression is significantly increased in degenerative nucleus pulposus tissue and shows a positive correlation with degeneration degree. Importantly, recent studies have demonstrated that METTL3-mediated m\n                    <jats:sup>6<\/jats:sup>\n                    A modification is able to promote the progression of IDD through multiple approaches, including extracellular matrix metabolism imbalance, inflammatory response, nucleus pulposus cell senescence and apoptosis, and mitochondrial dysfunction. Thus, METTL3 could represent a promising therapeutic target for IDD. This review systematically summarizes the latest advances regarding the role of METTL3 in IDD and underlying molecular mechanisms, and also highlights its potential translational implications.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1949071","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:10:07Z","timestamp":1790763007000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The m6A methyltransferase METTL3 in intervertebral disc degeneration: from molecular mechanisms to therapeutic potential"],"prefix":"10.3389","volume":"14","author":[{"given":"Yi-Chun","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Spine Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China","place":["Hengyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Song","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Danzhou People\u2019s Hospital","place":["Danzhou, Hainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, The First People\u2019s Hospital of Chenzhou","place":["Chenzhou, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Orthopedic Center, The First Affiliated Hospital, Hengyang Medical School, University of South China","place":["Hengyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China","place":["Hengyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e70053","DOI":"10.1002\/jsp2.70053","article-title":"Mechanism of intervertebral disc degeneration via the \u03b2-Catenin\/CCL2 pathway in Sox9 conditional knockout mice","volume":"8","author":"Aboushaala","year":"2025","journal-title":"JOR Spine"},{"key":"B2","doi-asserted-by":"publisher","first-page":"112728","DOI":"10.1016\/j.celrep.2023.112728","article-title":"Mitochondria-derived cell-to-cell communication","volume":"42","author":"AL Amir Dache","year":"2023","journal-title":"Cell Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1016\/j.cell.2015.08.011","article-title":"HNRNPA2B1 is a mediator of m6A-Dependent nuclear RNA processing events","volume":"162","author":"Alarc\u00f3n","year":"2015","journal-title":"Cell."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e07549","DOI":"10.1002\/advs.202507549","article-title":"H3K27ac is essential for human naive pluripotency modulated by m6A-Driven EP300 expression","volume":"12","author":"An","year":"2025","journal-title":"Adv. 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