Ferroptosis in endodontic pathobiology: Emerging evidence, mechanistic rationale, and translational uncertainties.

Authors

Anna Parviainen, Franklin Tay, Yuan-Yuan Li

Published in

Journal of endodontics. Oct 13, 2026. Epub Oct 13, 2026.

Abstract

Ferroptosis is an iron-dependent form of regulated cell death characterized by lipid peroxidation and impaired antioxidant defense. Its defining biochemical features, including iron-redox imbalance and lipid peroxide accumulation, overlap with biological conditions present in infected, hypoxic, and cytokine-rich endodontic tissues. This narrative review examined the potential role of ferroptosis in endodontic pathobiology, with emphasis on separating direct endodontic evidence from indirect or extrapolated oral evidence.
Electronic searches were performed in PubMed, Scopus, and Web of Science using terms related to ferroptosis, endodontics, pulpitis, apical periodontitis, dental pulp, root canal infection, Enterococcus faecalis, periodontal ligament, ferritinophagy, iron metabolism, lipid peroxidation, and major ferroptosis-related regulators. Ferroptosis-associated papers were classified according to proximity to endodontic disease and strength of evidence.
Current evidence suggests that ferroptosis-associated pathways may participate in pulpitis and apical periodontitis. Direct evidence is strongest for active pulpitis and apical periodontitis, where ferroptosis-related changes have been reported in human tissues, animal models, and endodontic-relevant cell systems, including dental pulp fibroblasts, dental pulp cells, dental pulp stem cells, endothelial cells, and macrophages. Extrapolated evidence from periodontitis, periodontal ligament cells, oral bone models, and dental stem-cell studies provides biological context but does not establish causation in endodontic disease. Evidence for complete pulp necrosis, inflammatory root resorption, post-treatment healing, and regenerative endodontics is indirect, limited, or absent.
Ferroptosis-associated pathways represent a credible but still emerging area of endodontic pathobiology. Current evidence suggests a possible contributory role in pulpal and periapical inflammation, but causal relevance, disease-stage specificity, and clinical significance remain unresolved. Future studies should use polymicrobial or infected-dentin models, human tissue validation, standardized ferroptosis criteria, and longitudinal intervention designs before ferroptosis-related mechanisms can be translated into endodontic diagnosis, treatment, or regenerative strategies.

PMID:
42869377
Bibliographic data and abstract were imported from PubMed on 14 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.