Document Type

Article

Publication Title

International Journal of Molecular Sciences

Department

Biomedical Sciences

ISSN

14220067

Volume

26

Issue

7

DOI

10.3390/ijms26073225

First Page

1

Last Page

22

Publication Date

3-30-2025

Abstract

Although periodontal disease (PD) is reported to be associated with changes in various genes and proteins in both invading bacteria and the host, its molecular mechanism of pathogenesis remains unclear. Changes in immune and inflammatory genes play a significant role in PD pathogenesis. Some reports relate alterations in cellular epigenetic patterns to PD characteristics, while several high-throughput analyses indicate thousands of differentially methylated genes in both PD patients and controls. Furthermore, changes in DNA methylation patterns in inflammation-related genes have been linked to the efficacy of periodontal therapy, as demonstrated by findings related to the cytochrome C oxidase II gene. Distinct DNA methylation patterns in mesenchymal stem cells from PD patients and controls persisted despite the reversal of phenotypic PD. Methyl groups for DNA methylation are supplied by S-adenosylmethionine, which is synthesized with the involvement of folate, an essential nutrient known to play a role in maintaining mitochondrial homeostasis, reported to be compromised in PD. Folate may benefit PD through its antioxidant action against reactive oxygen and nitrogen species that are overproduced by dysfunctional mitochondria. As such, DNA methylation, dietary folate, and mitochondrial quality control may interact in PD pathogenesis. In this narrative/hypothesis review, we demonstrate how PD is associated with changes in mitochondrial homeostasis, which may, in turn, be improved by folate, potentially altering the epigenetic patterns of immune and inflammatory genes in both the nucleus and mitochondria. Therefore, a folate-based dietary intervention is recommended for PD prevention and as an adjunct therapy. At the same time, further research is needed on the involvement of epigenetic mechanisms in the beneficial effects of folate on PD studies.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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