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

Tooth extraction socket healing is impaired in diabetes. We investigated whether the RNA-methyltransferase METTL3 could rescue this defect in an experimental animal study. 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. 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). 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.