Abstract

Background Periodontitis, a chronic inflammatory disease, represents the primary cause of tooth loss in Chinese adults. Wilms tumor 1‐associating protein (WTAP) is a key component of the N6‐methyladenosine (m6A) methyltransferase complex, and has an unclear role in periodontitis pathogenesis, particularly concerning its regulatory functions in periodontal ligament stem cells (PDLSCs). Methods The target gene was identified through the GES260558 dataset and Genecards database. Gene expression was measured using reverse transcription‐quantitative PCR (RT‐qPCR) and western blot. Periodontitis‐derived PDLSCs (P‐PDLSCs) were isolated and identified by alkaline phosphatase (ALP) staining, oil red O staining, and flow cytometry. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) levels, γ‐H2AX and SA‐β‐gal positive cells, and the expression of p53 and p16 were applied to reflect oxidative stress and cell senescence. Osteogenic differentiation was assessed by ALP activity, alizarin red S (ARS) staining, and related gene expression. The m6A‐dependent regulation of tumor protein p53 binding protein 1 (TP53BP1) mRNA by WTAP was confirmed using methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and Actinomycin D (Act D) assays. Results WTAP was identified as a candidate gene that was upregulated in periodontitis gingival tissues. Isolated P‐PDLSCs retained normal multilineage differentiation potential. WTAP knockdown significantly reduced senescence and oxidative stress in P‐PDLSCs while enhancing osteogenic differentiation. Mechanistically, WTAP mediated the m6A modification of TP53BP1 mRNA, and the effects of WTAP on P‐PDLSC senescence, oxidative stress, and osteogenic differentiation were dependent on TP53BP1. Conclusion The WTAP/TP53BP1 axis impairs periodontal tissue regeneration by promoting P‐PDLSC senescence an