Melatonin could alleviate the dysregulation of metabolic reprogramming in periodontitis—implications in host modulatory therapy

Abstract

Periodontitis is an infectious disease of the tooth-supporting apparatus characterized by connective tissue breakdown and alveolar bone resorption ultimately resulting in tooth loss. A chronic immune response and jeopardized oxidant–antioxidant balance are cardinal features in the pathobiology of periodontitis. The resident cells of the periodontium are known to undergo metabolic changes in the pathogenesis of periodontitis. The principal cellular fraction of the periodontal ligament space in states of health, disease, repair, and regeneration is the periodontal ligament stem cells (PDLSCs). Although these cells are believed to adapt well to bacterial infections, a recent in vitro study has shed light on the metabolic changes in these stem cells infected with Porphyromonas gingivalis lipopolysaccharide. The findings of the study demonstrated elevated levels of Krebs cycle enzymes, succinate, and hypoxia-inducible factor 1 alpha (HIF-alpha) in the stem cells following P. gingivalis infection. In this context, we hypothesize a potential role that could be played by melatonin, an indoleamine molecule that has been found to play a significant role in periodontal homeostasis. It has been proposed that exogeneous melatonin supplementation in periodontitis could help in targeting metabolic dysregulation as melatonin is endowed with potent anti-inflammatory and antioxidant properties. Melatonin could also help in decreasing succinate production in the PDLSC by increasing alpha-ketoglutarate generation and could inhibit stabilization of HIF-alpha. Melatonin-mediated conversion of proinflammatory M1 macrophage to anti-inflammatory M2 macrophage phenotype could help in the resolution of periodontal disease and foster healing mechanisms in the diseased periodontium.