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VOLUME 12 , ISSUE 2 ( March-April, 2021 ) > List of Articles

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Melatonin could Alleviate the Dysregulation of Metabolic Reprogramming in Periodontitis—Implications in Host Modulatory Therapy

Thodur M Balaji, Saranya Varadarajan, Debasish Bandyopadhyay, Raghunathan Jagannathan, CJ Venkatakrishnan, Ashok K Bhati, A Thirumal Raj, Swaminathan Rajendiran, Shankargouda Patil

Keywords : Hypothesis, Melatonin, Metabolic dysregulation, Periodontitis

Citation Information : Balaji TM, Varadarajan S, Bandyopadhyay D, Jagannathan R, Venkatakrishnan C, Bhati AK, Raj AT, Rajendiran S, Patil S. Melatonin could Alleviate the Dysregulation of Metabolic Reprogramming in Periodontitis—Implications in Host Modulatory Therapy. World J Dent 2021; 12 (2):166-170.

DOI: 10.5005/jp-journals-10015-1823

License: CC BY-NC 4.0

Published Online: 00-04-2021

Copyright Statement:  Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.


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.


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  1. Nanci A, Bosshardt DD. Structure of periodontal tissues in health and disease*. Periodontol 2000 2006;40(1):11–28. DOI: 10.1111/j.1600-0757.2005.00141.x.
  2. Löe H, Theilade E, Jensen SB. Experimental gingivitis in man. J Periodontol 1965;36(3):177–187. DOI: 10.1902/jop.1965.36.3.177.
  3. Armitage GC, Cullinan MP. Comparison of the clinical features of chronic and aggressive periodontitis. Periodontol 2000 2010;53(1):12–27. DOI: 10.1111/j.1600-0757.2010.00353.x.
  4. Scannapieco FA. Position paper of the American Academy of Periodontology: periodontal disease as a potential risk factor for systemic diseases. J Periodontol 1998;69:841–850. Im Internet: http://www.ncbi.nlm.nih.gov/pubmed/9706864.
  5. Grossi SG, Genco RJ. Periodontal disease and diabetes mellitus: a two-way relationship. Ann Periodontol 1998;3(1):51–61. DOI: 10.1902/annals.1998.3.1.51.
  6. Offenbacher S, Katz V, Fertik G, et al. Periodontal infection as a possible risk factor for preterm low birth weight. J Periodontol 1996;67(10s):1103–1113. DOI: 10.1902/jop.1996.67.10s.1103.
  7. Bodet C, Chandad F, Grenier D. Potentiel pathogénique de porphyromonas gingivalis, Treponema denticola et Tannerella forsythia, le complexe bactérien rouge associé à la parodontite. Pathol Biol 2007;55(3-4):154–162. DOI: 10.1016/j.patbio.2006.07.045.
  8. Kinane DF, Lappin DF. Immune processes in periodontal disease: a review. Ann Periodontol 2002;7(1):62–71. DOI: 10.1902/annals.2002.7.1.62.
  9. Page RC. The pathobiology of periodontal diseases may affect systemic diseases: inversion of a paradigm. Ann Periodontol 1998;3(1):108–120. DOI: 10.1902/annals.1998.3.1.108.
  10. Wang Y, Andrukhov O, Rausch-Fan X. Oxidative stress and antioxidant system in periodontitis. Front Physiol 2017. 8. DOI: 10.3389/fphys.2017.00910.
  11. Zhang H, Wang D, Li M, et al. Metabolic and proliferative state of vascular adventitial fibroblasts in pulmonary hypertension is regulated through a MicroRNA-124/PTBP1 (polypyrimidine tract binding protein 1)/pyruvate kinase muscle axis. Circulation 2017;136(25):2468–2485. DOI: 10.1161/CIRCULATIONAHA.117.028069.
  12. Su W, Shi J, Zhao Y, et al. Porphyromonas gingivalis triggers inflammatory responses in periodontal ligament cells by succinate-succinate dehydrogenase–HIF–1α axis. Biochem Biophys Res Commun 2020;522(1):184–190. DOI: 10.1016/j.bbrc.2019.11.074.
  13. Zhu W, Liang M. Periodontal ligament stem cells: current status, concerns, and future prospects. Stem Cells Int 2015;2015:1–11. DOI: 10.1155/2015/972313.
  14. Morandini ACF, Chaves Souza PP, Ramos-Junior ES, et al. Toll-like receptor 2 knockdown modulates interleukin (IL)-6 and IL-8 but not stromal derived factor-1 (SDF-1/CXCL12) in human periodontal ligament and gingival fibroblasts. J Periodontol 2013;84(4):535–544. DOI: 10.1902/jop.2012.120177.
  15. Liu J, Chen B, Bao J, et al. Macrophage polarization in periodontal ligament stem cells enhanced periodontal regeneration. Stem Cell Res Ther 2019;10(1):320. DOI: 10.1186/s13287-019-1409-4.
  16. Warburg O. The metabolism of carcinoma cells. J Cancer Res 1925;9(1):148–163. DOI: 10.1158/jcr.1925.148.
  17. Liberti MV, Locasale JW. The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci 2016;41(3):211–218. DOI: 10.1016/j.tibs.2015.12.001.
  18. Lachmandas E, Boutens L, Ratter JM, et al. Microbial stimulation of different toll-like receptor signalling pathways induces diverse metabolic programmes in human monocytes. Nat Microbiol 2017;2(3):16246. DOI: 10.1038/nmicrobiol.2016.246.
  19. Reiter RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev 1991;12(2):151–180. DOI: 10.1210/edrv-12-2-151.
  20. Shimozuma M, Tokuyama R, Tatehara S, et al. Expression and cellular localizaion of melatonin-synthesizing enzymes in rat and human salivary glands. Histochem Cell Biol 2011;135(4):389–396. DOI: 10.1007/s00418-011-0800-8.
  21. Madapusi BT, Rao SR. Preliminary evaluation of human gingiva as an extrapineal site of melatonin biosynthesis in states of periodontal health and disease. J Clin Diagnostic Res 2018;12:ZF01–ZF07. DOI: 10.7860/JCDR/2018/32451.11078.
  22. Mao L, Dauchy RT, Blask DE, et al. Melatonin suppression of aerobic glycolysis (Warburg effect), survival signalling and metastasis in human leiomyosarcoma. J Pineal Res 2016;60(2):167–177. DOI: 10.1111/jpi.12298.
  23. Xia Y, Chen S, Zeng S, et al. Melatonin in macrophage biology: current understanding and future perspectives. J Pineal Res 2019;66(2):e12547. DOI: 10.1111/jpi.12547.
  24. Liu Z, Gan L, Zhang T, et al. Melatonin alleviates adipose inflammation through elevating α-ketoglutarate and diverting adipose-derived exosomes to macrophages in mice. J Pineal Res 2018;64(1):e12455. DOI: 10.1111/jpi.12455.
  25. Ghosh AK, Naaz S, Bhattacharjee B, et al. Mechanism of melatonin protection against copper-ascorbate-induced oxidative damage in vitro through isothermal titration calorimetry. Life Sci 2017;180:123–136. DOI: 10.1016/j.lfs.2017.05.022.
  26. Reiter RJ, Mayo JC, Tan DX, et al. Melatonin as an antioxidant: under promises but over delivers. J Pineal Res 2016;61(3):253–278. DOI: 10.1111/jpi.12360.
  27. Ressmeyer A-R, Mayo JC, Zelosko V, et al. Antioxidant properties of the melatonin metabolite N 1-acetyl-5-methoxykynuramine (AMK): scavenging of free radicals and prevention of protein destruction. Redox Rep 2003;8(4):205–213. DOI: 10.1179/135100003225002709.
  28. Li J-H, Yu J-P, Yu H-G, et al. Melatonin reduces inflammatory injury through inhibiting NF-κB activation in rats with colitis. Mediators Inflamm 2005;2005(4):185–193. DOI: 10.1155/MI.2005.185.
  29. Murakami Y, Yuhara K, Takada N, et al. Effect of melatonin on cyclooxygenase-2 expression and nuclear factor-kappa B activation in RAW264.7 macrophage-like cells stimulated with fimbriae of Porphyromonas gingivalis. In Vivo 2011;25:641–647. Im Internet: http://www.ncbi.nlm.nih.gov/pubmed/21709008.
  30. Reiter RJ. Cytoprotective properties of melatonin: presumed association with oxidative damage and aging. Nutrition 1998;14(9):691–696. DOI: 10.1016/S0899-9007(98)00064-1.
  31. Kang H, Lee M-J, Park S, et al. Lipopolysaccharide-preconditioned periodontal ligament stem cells induce M1 polarization of macrophages through extracellular vesicles. Int J Mol Sci 2018;19(12):3843. DOI: 10.3390/ijms19123843.
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