Emerging roles of m6A modification in endodontic diseases: a systematic review.

AIM: This review aims to synthesize and evaluate the evidence on the role of N6-methyladenosine (m6A) modification in pathogenesis, progression, and tissue repair of endodontic diseases, focusing on its regulatory functions in dental stem cells.

METHODS

Two reviewers independently searched four databases for studies published by May 2025. The protocol was registered with PROSPERO (CRD420251233698). The certainty of findings was assessed using the CERQual approach.

RESULTS

Of 680 initial records, 27 studies were included. Findings demonstrated that m6A modification dynamically regulates enamel/root development, osteogenic/odontogenic differentiation of dental stem cells, and inflammatory responses in endodontic diseases. Five key themes were identified: pulpitis pathogenesis and repair, apical periodontitis pathogenesis and repair, and tooth development/pulp regeneration. Mechanistically, in pulpitis, METTL3 exacerbates inflammation via NF-κB/MAPK pathways, whereas FTO aggravates bone destruction in apical periodontitis. M6A regulates stem cell differentiation by modulating osteogenic/odontogenic gene expression and lncRNA/miRNA networks. METTL3 promotes tissue repair by stabilizing target mRNAs, while FTO enhances RUNX2 splicing. M6A regulates tooth morphogenesis through WTAP-SHH and METTL3-NFIC pathways.

CONCLUSIONS

This review establishes m6A modification as an important epitranscriptomic regulator that modulates inflammation and repair in endodontic diseases. Further clinical studies are needed to validate these mechanisms and their therapeutic potential.