Prophylactic Supplement with Melatonin Successfully Suppresses the Pathogenesis of Periodontitis through Normalizing RANKL/OPG Ratio and Depressing the TLR4/MyD88 Signaling Pathway.

Prophylactic Supplement with Melatonin Successfully Suppresses the Pathogenesis of Periodontitis through Normalizing RANKL/OPG Ratio and Depressing the TLR4/MyD88 Signaling Pathway.

J Pineal Res. 2017 Dec 23;:

Authors: Renn TY, Huang YK, Feng SW, Wang HW, Lee WF, Lin CT, Burnouf T, Chen LY, Kao PF, Chang HM

Abstract
Periodontitis (PD) is an inflammatory disease characterized by gingival inflammation and resorption of alveolar bone. Impaired receptor activator of nuclear factor-kappa B ligand/osteoprotegerin (RANKL/OPG) signaling caused by enhanced production of pro-inflammatory cytokines plays an essential role in the pathogenesis of PD. Considering melatonin possesses significant anti-inflammatory property, present study aims to determine whether prophylactic treatment with melatonin would effectively normalize RANKL/OPG signaling, depress toll-like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88) mediated pro-inflammatory cytokine activation, and successfully suppress the pathogenesis of PD. PD was induced in adult rats by placing the ligature at molar subgingival regions. Fourteen days before PD induction, 10, 50, or 100 mg/kg of melatonin were intraperitoneally injected for consecutive 28 days. Biochemical and enzyme-linked immunosorbent assay were used to detect TLR4/MyD88 activity, RANKL, OPG, interleukin 1β, interleukin 6, and tumor necrosis factor-α levels, respectively. The extent of bone loss, bone mineral intensity, and calcium intensity were further evaluated by scanning electron microscopy, micro-computed tomography and energy-dispersive X-ray spectroscopy. Results indicated that high RANKL/OPG ratio, TLR4/MyD88 activity and pro-inflammatory cytokine levels were detected following PD. Impaired biochemical findings paralleled well with severe bone loss and reduced calcium intensity. However, in rats pre-treated with melatonin, all above parameters were successfully returned to nearly normal levels with maximal change observed in rats receiving 100 mg/kg. As prophylactic treatment with melatonin effectively normalizes RANKL/OPG signaling by depressing TLR4/MyD88 mediated pro-inflammatory cytokine production, dietary supplement with melatonin may serve as an advanced strategy to strengthen oral health to counteract PD-induced destructive damage. This article is protected by copyright. All rights reserved.

PMID: 29274168 [PubMed - as supplied by publisher]

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