{"title":"mettl3介导的m6A调控GDF11促进糖尿病大鼠眼窝愈合","authors":"Ding Guo, Bin Zhang","doi":"10.2147/DMSO.S536806","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Tooth extraction socket healing is impaired in diabetes. We investigated whether the RNA-methyltransferase METTL3 could rescue this defect in an experimental animal study.</p><p><strong>Methods: </strong>Twelve-week-old male GK and Wistar rats received lentiviral overexpression or knockdown of METTL3 in the extraction socket. Socket healing was evaluated by micro-CT, histology and Quantitative real-time PCR (RT-qPCR). RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were performed to study the interaction between METTL3 and GDF11.</p><p><strong>Results: </strong>GK rats exhibited significantly lower body weight and METTL3 expression compared to Wistar rats (p<0.001). Micro-CT showed a 50% decrease in BV/TV versus diabetic controls (P < 0.001), accompanied by lower Tb.N and higher Tb.Sp (<i>p</i> < 0.001). Overexpression of METTL3 enhanced tooth extraction socket healing in GK rats, as evidenced by improved bone trabeculae formation and soft tissue healing (<i>p</i><0.001). METTL3 increased GDF11 expression and stability through m<sup>6</sup>A modification at a specific site (<i>p</i><0.001). Knockdown of GDF11 partially reversed the tooth extraction socket healing effects of METTL3 overexpression (<i>p</i><0.01).</p><p><strong>Conclusion: </strong>METTL3-mediated m<sup>6</sup>A methylation of GDF11 enhances socket healing in diabetic rats, identifying METTL3 as a potential therapeutic target for oral wound repair in diabetes.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"18 ","pages":"3505-3514"},"PeriodicalIF":3.0000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450055/pdf/","citationCount":"0","resultStr":"{\"title\":\"METTL3-Mediated m<sup>6</sup>A Regulation of GDF11 Promotes Socket Healing in Diabetic Rats.\",\"authors\":\"Ding Guo, Bin Zhang\",\"doi\":\"10.2147/DMSO.S536806\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Tooth extraction socket healing is impaired in diabetes. We investigated whether the RNA-methyltransferase METTL3 could rescue this defect in an experimental animal study.</p><p><strong>Methods: </strong>Twelve-week-old male GK and Wistar rats received lentiviral overexpression or knockdown of METTL3 in the extraction socket. Socket healing was evaluated by micro-CT, histology and Quantitative real-time PCR (RT-qPCR). RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were performed to study the interaction between METTL3 and GDF11.</p><p><strong>Results: </strong>GK rats exhibited significantly lower body weight and METTL3 expression compared to Wistar rats (p<0.001). Micro-CT showed a 50% decrease in BV/TV versus diabetic controls (P < 0.001), accompanied by lower Tb.N and higher Tb.Sp (<i>p</i> < 0.001). Overexpression of METTL3 enhanced tooth extraction socket healing in GK rats, as evidenced by improved bone trabeculae formation and soft tissue healing (<i>p</i><0.001). METTL3 increased GDF11 expression and stability through m<sup>6</sup>A modification at a specific site (<i>p</i><0.001). Knockdown of GDF11 partially reversed the tooth extraction socket healing effects of METTL3 overexpression (<i>p</i><0.01).</p><p><strong>Conclusion: </strong>METTL3-mediated m<sup>6</sup>A methylation of GDF11 enhances socket healing in diabetic rats, identifying METTL3 as a potential therapeutic target for oral wound repair in diabetes.</p>\",\"PeriodicalId\":11116,\"journal\":{\"name\":\"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy\",\"volume\":\"18 \",\"pages\":\"3505-3514\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450055/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/DMSO.S536806\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DMSO.S536806","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
METTL3-Mediated m6A Regulation of GDF11 Promotes Socket Healing in Diabetic Rats.
Purpose: Tooth extraction socket healing is impaired in diabetes. We investigated whether the RNA-methyltransferase METTL3 could rescue this defect in an experimental animal study.
Methods: Twelve-week-old male GK and Wistar rats received lentiviral overexpression or knockdown of METTL3 in the extraction socket. Socket healing was evaluated by micro-CT, histology and Quantitative real-time PCR (RT-qPCR). RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were performed to study the interaction between METTL3 and GDF11.
Results: GK rats exhibited significantly lower body weight and METTL3 expression compared to Wistar rats (p<0.001). Micro-CT showed a 50% decrease in BV/TV versus diabetic controls (P < 0.001), accompanied by lower Tb.N and higher Tb.Sp (p < 0.001). Overexpression of METTL3 enhanced tooth extraction socket healing in GK rats, as evidenced by improved bone trabeculae formation and soft tissue healing (p<0.001). METTL3 increased GDF11 expression and stability through m6A modification at a specific site (p<0.001). Knockdown of GDF11 partially reversed the tooth extraction socket healing effects of METTL3 overexpression (p<0.01).
Conclusion: METTL3-mediated m6A methylation of GDF11 enhances socket healing in diabetic rats, identifying METTL3 as a potential therapeutic target for oral wound repair in diabetes.
期刊介绍：
An international, peer-reviewed, open access, online journal. The journal is committed to the rapid publication of the latest laboratory and clinical findings in the fields of diabetes, metabolic syndrome and obesity research. Original research, review, case reports, hypothesis formation, expert opinion and commentaries are all considered for publication.
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