METTL3-Mediated m6A Regulation of GDF11 Promotes Socket Healing in Diabetic Rats

Ding Guo,1,2 Bin Zhang3 1Graduate School, Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China; 2Department of Stomatology, Shanghai Eighth People’s Hospital, Shanghai, People’s Republic of China; 3Department of Stomatology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of ChinaCorrespondence: Bin Zhang, Department of Stomatology, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, Liaoning, People’s Republic of China, Email [email protected]: 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.Keywords: diabetes, tooth extraction socket healing, METTL3, GDF11, m6A modification