GATA-1-driven TOMM20-mediated mitophagy regulates PDLSCs osteogenesis and enhances periodontal bone regeneration.

Periodontitis-induced periodontal bone defect is a key clinical challenge, and the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) is critical for bone repair. This study explored the role of the GATA-1-TOMM20-mitophagy axis in PDLSC osteogenic differentiation and periodontal bone repair. In a rat periodontitis model, TOMM20 expression was downregulated, accompanied by reduced bone volume/trabecular thickness (BV/TV/Tb.Th) and increased alveolar bone resorption (ABC-CEJ). TOMM20 overexpression (OE-TOMM20) ameliorated these bone defects, promoted mitophagy (reduced P62, increased LC3b/Beclin1), and enhanced PDLSC osteogenic differentiation (upregulated RUNX2/ALP/OCN, increased alizarin red/ALP staining), which was abolished by the autophagy inhibitor 3-MA. Genecards/JASPAR predicted GATA-1 as a top transcription factor for TOMM20. ChIP-PCR confirmed GATA-1 directly bound the TOMM20 promoter. GATA-1 overexpression upregulated TOMM20, while GATA-1 silencing downregulated it. Functional rescue experiments showed OE-GATA-1-induced mitophagy and PDLSC osteogenesis were reversed by TOMM20 silencing or 3-MA. In conclusion, GATA-1 transcriptionally activates TOMM20 to induce mitophagy, thereby promoting PDLSC osteogenic differentiation and periodontal bone repair, providing a potential therapeutic target for periodontitis.