Ferroptosis and Periodontal Tissue Destruction: What We Currently Know

Background: Periodontitis is a disease characterized by the destruction of periodontal tissue and tooth loss. The molecular mechanisms behind this disease, however, are not clearly understood. Ferroptosis is an iron-dependent, lipid peroxidation-driven form of regulated cell death that seems to play a role in periodontal pathogenesis by increasing oxidative stress and reducing tissue regeneration. Objective: The current narrative review aims to summarize current knowledge of the involvement of ferroptosis in periodontal tissue destruction and potentially to identify new targets of therapy. Methods: A comprehensive search of PubMed, Embase, and Web of Science databases was conducted. Original human, animal, and in vitro studies published in English were selected. Data on experimental models, molecular markers, and key outcomes were extracted and synthesized in the review. Results: After screening, four studies were identified and selected. Ferroptosis activation in periodontal ligament fibroblasts, stem cells, and gingival tissues was associated with increased ACSL4 and decreased GPX4 expression, iron accumulation, and oxidative stress. The administration of Ferrostatin-1 or antioxidants like curcumin seemed to reduce inflammation and alveolar bone loss in vivo. Transcriptomic analyses further revealed immune-related ferroptosis gene signatures in human periodontitis tissues. Conclusions: Ferroptosis represents a crucial mechanism in periodontal tissue destruction through not yet completely understood. Understanding these molecular pathways could be the key to developing new therapeutic strategies for periodontal treatment.