{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:02:36Z","timestamp":1787313756492,"version":"build-2736575974"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82125006,U24A20710"],"award-info":[{"award-number":["82125006,U24A20710"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020756","name":"West China School of Stomatology, Sichuan University","doi-asserted-by":"crossref","award":["RCDWJS2025-2"],"award-info":[{"award-number":["RCDWJS2025-2"]}],"id":[{"id":"10.13039\/100020756","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:p>\n                    Methyltransferase-like 5 (METTL5) is a methyltransferase responsible for rRNA N6-methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) modification, mutations in which are associated with skeletal abnormalities and cognitive deficits. Despite METTL5\u2019s clinical relevance, the molecular mechanisms underlying METTL5-related genetic disorders remain poorly understood. In this study, we demonstrated that\n                    <jats:italic>Mettl5<\/jats:italic>\n                    KO led to reduced bone mass and smaller body size in mice and impaired the osteogenic differentiation of mesenchymal stem cells. Mechanistically,\n                    <jats:italic>Mettl5<\/jats:italic>\n                    deficiency decreased the translation efficiency of oxidative stress\u2013responsive serine-rich protein 1 mRNA, downregulated the expression of key antioxidant genes, and diminished antioxidant capacity. Importantly, administration of the antioxidant N-acetylcysteine (NAC) partially rescued skeletal defects in\n                    <jats:italic>Mettl5<\/jats:italic>\n                    -KO mice. These findings reveal a critical role for METTL5 in antioxidant defense and suggest that NAC supplementation may represent a promising therapeutic strategy for METTL5-related disorders.\n                  <\/jats:p>\n                  <jats:p>METTL5 maintains bone health through antioxidant regulation and its loss leads to bone loss, while antioxidant therapy restores bone mass, offering hope for METTL5-related disorders.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1172\/jci.insight.194068","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T18:00:48Z","timestamp":1778176848000},"source":"Crossref","is-referenced-by-count":3,"title":["METTL5 deficiency impairs osteogenesis through OSER1-dependent antioxidant regulation"],"prefix":"10.1172","volume":"11","author":[{"given":"Kexin","family":"Lei","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiwen","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, and National Clinical Research 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