Epigenetic Mechanisms in Periodontics: Molecular Insights, Clinical Applications and Therapeutic Potential

Abstract Periodontitis is a chronic inflammatory disease in which microbial dysbiosis interacts with the host immune response to drive tissue destruction. While genetics and environment both contribute to disease susceptibility, epigenetic regulation provides a dynamic layer that mediates how external exposures (e.g. bacteria, smoking, diabetes) influence gene expression without altering DNA sequence. In periodontal tissues, DNA methylation, histone modifications, and non-coding RNAs (miRNAs, lncRNAs, circRNAs) have been implicated in modulating inflammation, immune response, and bone metabolism. This review synthesizes current knowledge on epigenetic alterations observed in periodontitis, evaluates candidate biomarkers and therapeutic strategies (epidrugs), discusses challenges in clinical translation, and proposes directions for future research. We highlight that although many studies report differential methylation or miRNA patterns, heterogeneity in sample types, small cohorts, cross-sectional design, and lack of functional validations limit translational impact. Advances in single-cell epigenomics, spatial profiling, CRISPR-based epigenetic editing, and localized delivery systems may overcome these barriers. Ultimately, integrating epigenetic insights into periodontology could enable personalized diagnostics, risk stratification, and adjunctive regenerative therapies.