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

Dec 13, 2025Biochemical and biophysical research communications

How GATA-1 and TOMM20 control mitochondrial recycling to support stem cell bone formation and improve gum bone healing

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Abstract

Downregulation of TOMM20 in a rat periodontitis model is associated with reduced bone volume and increased alveolar bone resorption.

TOMM20 overexpression improves bone defects and promotes mitophagy.
Mitophagy enhancement is indicated by reduced P62 and increased LC3b/Beclin1 levels.
Osteogenic differentiation of periodontal ligament stem cells is enhanced through the upregulation of RUNX2, ALP, and OCN.
Inhibition of autophagy with 3-MA abolishes the effects of TOMM20 overexpression on bone repair.
GATA-1 is identified as a key transcription factor that activates TOMM20.
GATA-1 overexpression increases TOMM20 levels, while its silencing decreases them.

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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.

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

Abstract

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