Impact of Epigenetic Alterations in the Development of Oral Diseases

Abstract

Epigenetic mechanisms alter gene expression and regulate vital cellular processes that contribute to the onset and progression of major dental diseases. Their reversible character may prove beneficial for therapeutic targeting. This review aims to provide an update on the main epigenetic changes that contribute to the pathogenesis of Oral Squamous Cell Carcinoma (OSCC), pulpitis and periodontitis as well as dental caries and congenital orofacial malformations, in an effort to identify potential therapeutic targets. We undertook a structured search of bibliographic databases (PubMed and MEDLINE) for peer-reviewed epigenetic research studies focused on oral diseases in the last ten years. A qualitative content analysis was performed in screened papers and a critical discussion of main findings is provided. Several epigenetic modifications have been associated with OSCC pathogenesis, including promoter methylation of genes involved in DNA repair, cell cycle regulation and proliferation leading to malignant transformation. Additionally, epigenetic inactivation of tumor suppressor genes, overexpression of histone chaperones and several microRNAs are implicated in OSCC aggressiveness. Changes in the methylation patterns of IFN-γ and trimethylation of histone Η3Κ27 have been detected in pulpitis, along with an aberrant expression of several microRNAs, mainly affecting cytokine production. Chronic periodontal disease has been associated with modifications in the methylation patterns of Toll-Like Receptor 2, Prostaglandin synthase 2, E-cadherin and some inflammatory cytokines, along with the overexpression of miR-146a and miR155. Furthermore, DNA methylation was found to regulate amelogenesis and has been implicated in the pathogenesis of dental caries as well as in several congenital orofacial malformations. Strong evidence indicates that epigenetic changes participate in the pathogenesis of oral diseases and epigenetic targeting may be considered as a complementary therapeutic scheme to the current management of oral health.