Skip to main content

Advertisement

SpringerLink
Log in

Effect of topical application of melatonin to the gingiva on salivary osteoprotegerin, RANKL and melatonin levels in patients with diabetes and periodontal disease

  • Original Article
  • Published:
Odontology Aims and scope Submit manuscript

Abstract

This cross-section study was designed to assess the effect of topical application of melatonin to the gingiva on salivary RANKL, osteoprotegrin (OPG) and melatonin levels as well as plasma melatonin in 30 patients with diabetes and periodontal disease and in a control group of 30 healthy subjects. Salivary RANKL and OPG were measured by enzyme-linked immunosorbent assay and salivary and plasma melatonin by radioimmunoassay using commercial kits. Periodontograms were performed using the Florida Probe®. Diabetic patients were treated with topical application of melatonin (1 % orabase cream formula) once daily for 20 days. Patients with diabetes showed significantly higher mean levels of salivary RANKL than healthy subjects as well as significantly lower values of salivary OPG and salivary and plasma melatonin. After treatment with melatonin, there was a statistically significant decrease of the gingival index, pocket depth and salivary levels of RANKL, and a significant rise in salivary values of OPG. Changes of salivary OPG levels before and after topical melatonin treatment correlated significantly with changes in the gingival index and pocket depth. Treatment with topical melatonin was associated with an improvement in the gingival index and pocket depth, a reduction in salivary concentrations of RANKL and increase in salivary concentrations of OPG, which indicates that melatonin has a favorable effect in slowing osteoclastogenesis, improving the quality of alveolar bone and preventing the progression of periodontal disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ridgeway EE. Periodontal disease: diagnosis and management. J Am Acad Nurse Pract. 2000;12:79–84.

    Article  PubMed  Google Scholar 

  2. Loesche WJ. Bacterial mediators in periodontal disease. Clin Infect Dis. 1993;16(Suppl 4):S203–10.

    Article  PubMed  Google Scholar 

  3. Yasuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 1998;95:3597–602.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Mogi M, Otogoto J, Ota N, Togari A. Differential expression of RANKL and osteoprotegerin in gingival crevicular fluid of patients with periodontitis. J Dent Res. 2004;83:166–9.

    Article  PubMed  Google Scholar 

  5. Lu HK, Chen YL, Chang HC, Li CL, Kuo My. Identification of the osteoprotegerin/receptor activator of nuclear factor-kappa B ligand system in gingival crevicular fluid and tissue of patients with chronic periodontitis. J Periodontal Res. 2006;41:354–60.

    Article  PubMed  Google Scholar 

  6. Vernal R, Chaparro A, Graumann R, Puente J, Valenzuela MA, Gamonal J. Levels of cytokine receptor activator of nuclear factor kappaB ligand in gingival crevicular fluid in untreated chronic periodontitis patients. J Periodontol. 2004;75:1586–91.

    Article  PubMed  Google Scholar 

  7. Khosla S. Minireview: The OPG/RANKL/RANK system. Endocrinology. 2001;142:5050–5.

    Article  PubMed  Google Scholar 

  8. Belibasakis GN, Bostanci N. The RANKL-OPG system in clinical periodontology. J Clin Periodontol. 2011. doi:10.1111/j.1600-051X.2011.01810.x.

    Google Scholar 

  9. Kajiya M, Giro G, Taubman MA, Han X, Mayer MP, Kawai T. Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease. J Oral Mocrobiol 2010; 2. doi:10.3402/jom.v20.5532.

  10. Boyce BF, Xing L. The RANKL/RANK/OPG pathway. Curr Osteoporos Rep. 2007;5:98–104.

    Article  PubMed  Google Scholar 

  11. Liu D, Xu JK, Figliomeni L, et al. Expression of RANKL and OPG mRNA in periodontal disease: possible involvement in bone destruction. Int J Mol Med. 2003;11:17–21.

    PubMed  Google Scholar 

  12. Crotti T, Smith MD, Hirsch R, et al. Receptor activator NF kappaB ligand [RANKL) and osteoprotegerin [OPG) protein expression in periodontitis. J Periodontal Res. 2003;38:380–7.

    Article  PubMed  Google Scholar 

  13. Stehle JH, Saade A, Rawashdeh O, et al. A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases. J Pineal Res. 2011;51:17–43.

    Article  PubMed  Google Scholar 

  14. Tan DX, Chen LD, Poeggeler B, et al. Melatonin: a potent endogenous hydroxyl radical scavenger. Endocr J. 1993;1:56–60.

    Google Scholar 

  15. Reiter RJ, Tan DX, Manchester LC, Qi W. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem Biophys. 2001;34:237–56.

    Article  PubMed  Google Scholar 

  16. Galano A, Tan DX, Reiter RJ. Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res. 2011;51:1–16.

    Article  PubMed  Google Scholar 

  17. Reiter RJ, Calvo JR, Karbownik M, Qi W, Tan DX. Melatonin and its relation to the immune system and inflammation. Ann NY Acad Sci. 2000;917:376–86.

    Article  PubMed  Google Scholar 

  18. Radogna F, Diederich M, Ghibelli L. Melatonin: a pleiotropic molecule regulating inflammation. Biochem Pharmacol. 2010;80:1844–52.

    Article  PubMed  Google Scholar 

  19. Cardinali DP, Ladizesky MG, Boggio V, Cutrera RA, Mautalen C. Melatonin effects on bone: experimental facts and clinical perspectives. J Pineal Res. 2003;34:81–7.

    Article  PubMed  Google Scholar 

  20. Sánchez-Barceló EJ, Mediavilla MD, Tan DX, Reiter RJ. Scientific basis for the potential use of melatonin in bone diseases: osteoporosis and adolescent idiopathic scoliosis. J Osteoporosis. 2010. doi:10.4061/2010/830231.

    Google Scholar 

  21. Park KH, Kang JW, Lee EM, et al. Melatonin promotes osteoblastic differentiation through the BMP/ERK/Wnt signaling pathways. J Pineal Res. 2011;51:187–94.

    Article  PubMed  Google Scholar 

  22. Zhang L, Su P, Xu C, et al. Melatonin inhibits adipogenesis and enhances osteogenesis of human mesenchymal stem cells by suppressing PPARy expression and enhancing Runx2 expression. J Pineal Res. 2011;49:364–72.

    Article  Google Scholar 

  23. Koyama H, Nakade O, Takada Y, Kaku T, Lau KH. Melatonin at pharmacologic doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Mineral Res. 2002;17:1219–29.

    Article  Google Scholar 

  24. Ostrowska Z, Ziora K, Kos-Kudta B, et al. Melatonin, the RANKL/RANK/OPG system, and bone metabolism in girls with anorexia nervosa. Endokrynol Pol. 2010;61:117–23.

    PubMed  Google Scholar 

  25. Satomura K, Tobiume S, Tokuyama R, et al. Melatonin at pharmacological doses enhances human osteoblastic differentiation in vitro and promotes mouse cortical bone formation in vivo. J Pineal Res. 2007;42:231–9.

    Article  PubMed  Google Scholar 

  26. Roth JA, Kim BG, Lin WL, Cho MI. Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem. 1999;274:22041–7.

    Article  PubMed  Google Scholar 

  27. Gómez-Moreno G, Guardia J, Ferrera MJ, Cutando A, Reiter RJ. Melatonin in diseases of the oral cavity. Oral Dis. 2009. doi:10.1111/j.1601-0825.2009.01610.x.

    PubMed  Google Scholar 

  28. Blasiak J, Kasznicki J, Drzewoski J, Pawlowska E, Szczepanska J, Reiter RJ. Perspectives on the use of melatonin to reduce cytotoxic and genotoxic effects of methacrylate-based dental materials. J Pineal Res. 2011;51:157–62.

    Article  PubMed  Google Scholar 

  29. Cutando A, Gómez-Moreno G, Villalba J, Ferrera MJ, Escames G, Acuña-Castroviejo D. Relationship between salivary melatonin levels and periodontal status in diabetic patients. J Pineal Res. 2003;35:239–44.

    Article  PubMed  Google Scholar 

  30. Miles A, Thomas DR, Grey JE, Pugh AJ. Salivary melatonin assay in laboratory medicine—longitudinal profiles of secretion in healthy men. Clin Chem. 1987;33:1957–9.

    PubMed  Google Scholar 

  31. Taylor GW. Bidirectional interrelationships between diabetes and periodontal diseases: an epidemiologic perspective. Ann Periodontol. 2001;6:99–112.

    Article  PubMed  Google Scholar 

  32. Bascones-Martinez A, Matesanz-Perez P, Escribano-Bermejo M, González-Moles MÁ, Bascones-Ilundain J, Meurman JH. Periodontal disease and diabetes—review of the literature. Med Oral Patol Oral Cir Bucal. 2011;16:e722–9.

    Article  PubMed  Google Scholar 

  33. Mealey BL, Oates TW. Diabetes mellitus and periodontal diseases. J Periodontol. 2006;77:1289–303.

    Article  PubMed  Google Scholar 

  34. World Health Organization. Oral health surveys: basic methods, 4th edition. Geneva: World Health Organization 1987. pp. 31–32.

  35. Shirakawa S, Tsuchiya S, Tsutsumi Y, et al. Time course of saliva and serum melatonin levels after ingestion of melatonin. Psychiatry Clin Neurosci. 1998;52:266–7.

    Article  PubMed  Google Scholar 

  36. Gómez-Moreno G, Cutando-Soriano A, Arana C, et al. Melatonin expression in periodontal disease. J Periodont Res. 2007;42:536–40.

    Article  PubMed  Google Scholar 

  37. Cutando A, Galindo P, Gómez-Moreno G, et al. Relationship between salivary melatonin and severity of periodontal disease. J Periodontol. 2006;77:1533–8.

    Article  PubMed  Google Scholar 

  38. Secchiero P, Corallini F, Pandolfi A, et al. An increased osteoprotegerin serum release characterizes the early onset of diabetes mellitus and may contribute to endothelial cell dysfunction. Am J Pathol. 2006;169:2236–44.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Galluzzi F, Stagi S, Salti R, et al. Osteoprotegerin serum levels in children with type 1 diabetes: a potential modulating role in bone status. Eur J Endocrinol. 2005;153:879–85.

    Article  PubMed  Google Scholar 

  40. Knudsen ST, Foss CH, Poulsen PL, Andersen NH, Mogensen CE, Rasmussen LM. Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications. Eur J Endocrinol. 2003;149:39–52.

    Article  PubMed  Google Scholar 

  41. Anand DV, Lahiri A, Lim E, Hopkins D, Corder R. The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects. J Am Coll Cardiol. 2006;47:1850–7.

    Article  PubMed  Google Scholar 

  42. Yamaguchi M, Takada R, Kambe S, et al. Evaluation of time-course changes of gingival crevicular fluid glucose levels in diabetics. Biomed Microdevices. 2005;7:53–8.

    Article  PubMed  Google Scholar 

  43. Silva JA, Lopes Ferrucci D, Peroni LA, et al. Periodontal disease-associated compensatory expression of osteoprotegerin is lost in type 1 diabetes mellitus and correlates with alveolar bone destruction by regulating osteoclastogenesis. Cells Tissues Organs. 2012. doi:10.1159/000330879.

    PubMed  Google Scholar 

  44. Duarte PM, Neto JB, Casati MZ, Sallum EA, Nociti FH Jr. Diabetes modulates gene expression in the gingival tissues of patients with chronic periodontitis. Oral Dis. 2007;13:594–9.

    Article  PubMed  Google Scholar 

  45. Cochran DL. Inflammation and bone loss in periodontal disease. J Periodontol. 2008;79(8 Suppl 1):1569–76.

    Article  PubMed  Google Scholar 

  46. Lakschevitz F, Aboodi G, Tenenbaum H, Glogauer M. Diabetes and periodontal diseases: interplay and links. Curr Diabetes Rev. 2011;7:433–9.

    Article  PubMed  Google Scholar 

  47. Nagorny C, Lyssenko V. Tired of diabetes genetics? Circadian rhythms and diabetes: the MTNR1B story? Curr Diab Rep. 2012;12:667–72.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Marta Pulido, MD, for editing the manuscript and editorial assistance.

Conflicts of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Special Care in Dentistry, School of Dentistry, University of Granada, Granada, Spain

    Antonio Cutando

  2. Department of Surgery, School of Dentistry, Faculty of Medicine, University of Salamanca, Salamanca, Spain

    Antonio López-Valverde & Joaquín de Vicente

  3. Department of Stomatology, University of Alfonso X, Madrid, Spain

    Rafael Gómez de Diego

  4. Department of Cellular and Structural Biology, The UT Health Science Center, San Antonio, TX, 78229-3900, USA

    Russell Reiter

  5. Centre Metropolitan of Pinos Puente, Granada, Spain

    María José Ferrera

  6. Departamento de Estomatología, Facultad de Odontología de la Universidad de Granada, Campus Universitario de Cartuja s/n, 18071, Granada, Spain

    Antonio Cutando

  7. Ramón y Cajal Hospital, Madrid, Spain

    María Herrero Fernández

Authors
  1. Antonio Cutando
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio López-Valverde
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rafael Gómez de Diego
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joaquín de Vicente
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Russell Reiter
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. María Herrero Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. María José Ferrera
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Cutando.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cutando, A., López-Valverde, A., de Diego, R.G. et al. Effect of topical application of melatonin to the gingiva on salivary osteoprotegerin, RANKL and melatonin levels in patients with diabetes and periodontal disease. Odontology 102, 290–296 (2014). https://doi.org/10.1007/s10266-013-0122-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10266-013-0122-5

Keywords

Search

Navigation