Epigenetics in susceptibility, progression, and diagnosis of periodontitis

Abstract

Periodontitis is characterized by irreversible destruction of periodontal tissue. At present, the accepted etiology of periodontitis is based on a three-factor theory including pathogenic bacteria, host factors, and acquired factors. Periodontitis development usually takes a decade or longer and is therefore called chronic periodontitis (CP). To search for genetic factors associated with CP, several genome-wide association study (GWAS) analyses were conducted; however, polymorphisms associated with CP have not been identified. Epigenetics, on the other hand, involves acquired transcriptional regulatory mechanisms due to reversibly altered chromatin accessibility. Epigenetic status is a condition specific to each tissue and cell, mostly determined by the responses of host cells to stimulations by local factors, like bacterial inflammation, and systemic factors such as nutrition status, metabolic diseases, and health conditions. Significantly, epigenetic status has been linked with the onset and progression of several acquired diseases. Thus, epigenetic factors in periodontal tissues are attractive targets for periodontitis diagnosis and treatments. In this review, we introduce accumulating evidence to reveal the epigenetic background effects related to periodontitis caused by genetic factors, systemic diseases, and local environmental factors, such as smoking, and clarify the underlying mechanisms by which epigenetic alteration influences the susceptibility of periodontitis.

Keywords: 5mC, 5-methylcytocine; AP, aggressive periodontitis; ATAC-seq, assay for transposase-accessible chromatin sequencing; CP, chronic periodontitis; DNA methylation; ECM, extracellular matrix; Epigenetics; Epigenome; GWAS, genome-wide association study; H3K27ac, acetylation of histone H3 lysine 27; H3K27me3, trimethylation of histone H3 lysine 27; H3K4me3, trimethylation of histone H3 lysine 4; H3K9ac, histone H3 lysine 9; HATs, histone acetyltransferases; HDACs, histone deacetylases; Histone modifications; LPS, lipopolysaccharide; PDL, periodontal ligament; Periodontal ligament; Periodontitis; ceRNA, competing endogenous RNA; lncRNAs, long ncRNAs; m6A, N6-methyladenosine; ncRNAs, non-coding RNAs; sEV, small extracellular vesicles.