{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:26:45Z","timestamp":1788960405278,"version":"build-2803163510"},"reference-count":141,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Periodontitis is a chronic inflammatory disease driven by dysbiotic biofilm and abnormal host adaptive immune responses, characterized by irreversible destruction of periodontal tissues. Recent studies indicate that ferroptosis\u2014a form of iron-dependent lipid peroxidation-mediated cell death\u2014is not a passive outcome of the disease process but rather an important active inducer and pathological amplifier in the development of periodontitis. This review synthesizes existing evidence to propose that ferroptosis acts as an important regulatory node within the pathological network of periodontitis, impairs epithelial barrier function, suppresses osteoblast differentiation and function, and amplifies pro-inflammatory signaling pathways through cell-type-specific mechanisms. Furthermore, ferroptosis exhibits complex cross-regulation with other cell death pathways (e.g., pyroptosis, apoptosis, autophagy), collectively forming a self-amplifying vicious cycle that persistently drives chronic inflammation and tissue destruction. Although iron death-targeting interventions, including iron chelators, GPX4 agonists, lipid peroxidation scavengers, natural bioactive compounds (e.g., curcumin, resveratrol), and nanodelivery systems, show promise in preclinical studies, the cell type specificity and context dependency of ferroptosis pose critical challenges for precise intervention. Therefore, this review positions ferroptosis as a pivotal node in the regulatory network of periodontal cell death, advocating for the development of stage-specific and cell-type-specific targeted strategies. This signifies a paradigm shift in periodontal therapy, transitioning from traditional antimicrobial approaches toward host-centered precision periodontal medicine.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1823915","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:43:56Z","timestamp":1777437836000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Ferroptosis: a promising therapeutic target for periodontitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuanyuan","family":"Li","sequence":"first","affiliation":[{"name":"Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, The Affiliated Stomatological Hospital, Southwest Medical University","place":["Luzhou, China"]},{"name":"Department of Prosthodontics, The Affiliated Stomatological Hospital of Southwest Medical University","place":["Luzhou, Sichuan, China"]},{"name":"Institute of Stomatology, 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