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

  • Biochem Biophys Res Commun. 2026 Jan 8:795:153121. doi: 10.1016/j.bbrc.2025.153121.
Qi Cai  1 ,  Zhizen Quan  1 ,  Xinyu Yang  1 ,  Chen Li  1 ,  Yu Chen  1 ,  Yibo Wei  2 ,  Yang Zhang  3 ,  Xiaogang Xu  4
Affiliations
  • 1. Department of Stomatology, The First Affiliated Hospital of Naval Medical University, No.168 Changhai Road, Yangpu District, Shanghai, 200433, China.
  • 2. Department of Stomatology, The First Affiliated Hospital of Naval Medical University, No.168 Changhai Road, Yangpu District, Shanghai, 200433, China. Electronic address: [email protected].
  • 3. Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China. Electronic address: [email protected].
  • 4. Department of Stomatology, The First Affiliated Hospital of Naval Medical University, No.168 Changhai Road, Yangpu District, Shanghai, 200433, China. Electronic address: [email protected].
PMID: 41389613 DOI: 10.1016/j.bbrc.2025.153121
Abstract

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.

Keywords
GATA-1; Mitophagy; Periodontal ligament stem cells; Periodontitis; TOMM20.
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