Heat Shock Protein 27 as a Candidate Mediator of Radiation-Induced Periodontitis: Mechanistic Rationale and Translational Perspectives

Radiation-induced periodontitis represents an underrecognized and mechanistically complex toxicity of head and neck radiotherapy, arising from the interplay of oxidative stress, inflammatory dysregulation, impaired bone remodeling, and epithelial barrier disruption. Despite its clinical relevance, the molecular determinants underlying inter-individual susceptibility remain poorly defined. Heat shock protein 27 (HSP27), a stress-inducible molecular chaperone, has emerged as a candidate mediator potentially linking biological pathways relevant to radiation-induced tissue injury, including redox regulation, cytoskeletal stability, DNA repair, and apoptosis control. However, no clinical or experimental study has directly evaluated HSP27 in radiation-induced periodontitis. Therefore, the proposed involvement of HSP27 in this setting should be interpreted as a biologically plausible, hypothesis-generating framework rather than evidence of a proven causal mechanism. Convergent but indirect evidence from periodontal biology, radiation-response models, inflammatory disease, and cellular stress systems suggests that HSP27 may plausibly influence periodontal tissue resilience and injury responses after radiotherapy. Therapeutic modulation of HSP27 may represent a potential investigational strategy to mitigate radiation-induced periodontitis, but this concept requires direct validation in periodontal cell-based, animal, organoid, and prospective clinical studies. This review synthesizes current mechanistic and translational evidence to evaluate HSP27 as a candidate mediator, biomarker, and investigational therapeutic target in radiation-induced periodontitis.