Ferroptosis in periodontitis: Mechanism, role, and therapeutic potential.

Abstract

Periodontitis is a chronic inflammatory disease initiated by plaque biofilm, characterized by progressive destruction of the periodontal supporting tissues. In addition to microbial factors, host immune response-mediated tissue damage plays a central role in disease progression. Recent studies have revealed that ferroptosis, an iron-dependent, lipid peroxidation-driven form of programmed cell death, plays a significant role in the pathological process of periodontitis. This review systematically analyzes the molecular regulatory mechanisms of ferroptosis, including dysregulation of iron metabolism, dysfunction of the glutathione/glutathione peroxidase 4 (GSH/GPX4) antioxidant system, and accumulation of lipid peroxidation. It focuses on how factors in the periodontitis microenvironment, such as iron overload, oxidative stress, and hypoxia, synergistically induce ferroptosis in periodontal ligament cells, gingival epithelial cells, osteoblasts, and other cell types, thereby contributing to soft tissue inflammation, disruption of the epithelial barrier, and alveolar bone resorption. The article summarizes evidence from cell experiments, animal models, and clinical studies, demonstrating that modulation of ferroptosis pathways can influence the progression of periodontitis. Finally, the potential of targeting ferroptosis as a novel therapeutic strategy is discussed, including the application of ferroptosis inhibitors, the development of nano-delivery systems, and synergistic effects with conventional treatments. A deeper understanding of the role of ferroptosis in periodontitis not only provides new insights into the disease pathology but also lays a theoretical foundation for the development of novel therapeutic approaches.