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ePaper created 2016-06-09, 15:16:05 | version 1.38.0
Journal of Oral Science & Rehabilitation 12 Volume 2 | Issue 2/2016 – Cortisol (also known as hydrocortisone) and otherglucocorticoids are increasedwhen mel- atonin is reduced. They are responsible for in- hibiting bone formationthrough direct actions on osteoblasts by blocking their recruitment anddifferentiation,andsubsequentlyinhibiting the production of Type I collagen. An increase in cortisol is also responsible for an increase in bone resorption via antagonism of the 1,25- dihydroxyvitamin D. Therefore, as melatonin increases,glucocorticoidsarereducedandtheir pro-resorptive effects are limited. – Melatonin also stimulates estrogen secretion and,therefore,limitstheassociateddeleterious effects of deficiency.33 I I . A c t i o n i n i m m u n e s y s t e m The role played bymelatonin inthe immune sys- tem is well documented.34 The effects of mela- tonin have been most widely studied in the con- text of depressed immune systems with the aim ofimproving immunodeficiencysituations. Mel- atonin regulates the apoptosis of B and T cells and has been reported to accelerate the produc- tion of leukocytes.35 In addition to the direct effect on cells of the im- mune system, melatonin reduces the synthesis ofprostaglandins,especiallyPGE-2;preventsthe translocation of nuclear factor-kappa B to the nucleus and its bindingto DNA,therebyreducing the up-regulation of a variety of pro-inflamma- torycytokines;36 inhibitsthe production ofadhe- sion molecules that promotes the adhesion of leukocytes to endothelial cells;37 and attenuates transendothelialcellmigrationandedema,which contribute to tissue damage.30 It also stimulates the release of interleukin-2 in Jurkat cells38 and interleukin-6 in peripheral blood mononuclear cells,39 while it inhibitsthe inflammatoryenzyme cyclooxygenase-2(COX-2)andbindstotheactive sitesofCOX-1andCOX-2.40 Therefore,melatonin can inhibit acute inflammatoryreaction and con- tribute to generating an immune reaction, mini- mizing the associated bone loss.30 I I I . A c t i o n o n f r e e r a d i c a l s Oneoftheprincipalbiologicalactionsofmelatonin isitswideantioxidantspectrumandpowerfulen- dogenous effect as a free-radical scavenger.41 Thus, it has an indirect reparative effect and pre- vents intracellular damage, protecting cells from free radicals and chemicalsubstances. Melatonin actsonoxygen-andnitrogen-derivedfreeradicals, including the highly toxic hydroxyl radical,42 per- oxynitrite anion43 and hypochlorous acid.44 In ad- dition to directly neutralizing free radicals and reactivespeciesofnitrogenandoxygen,melatonin stimulates other antioxidant enzymes, such as glutathione.45 At the bone level, these effects are of vital importance because osteoclasts secrete a wide varietyofmolecularagentsforbonedegradation. Free radicals are the highly secreted ones. Os- teoclasts generate superoxide anions during re- sorption that contribute to the degradative pro- cesses of the organic bone matrix. Other cell types, such as monocytes, macrophages and neutrophils,accumulateontheadjacentsurfaces of the bone in chronic inflammatory processes. These cells have the capacity to produce free radicals and, as previously mentioned, are able to stimulate osteoclastic response by liberating mediators (cytokines, tumor necrosis factors, etc.). Therefore, the use of anti-free-radical agents might be an adequate alternativetherapy forthese types ofpathologies, bylimiting osteo- clastic activation or free-radical production. Melatonin and periodontal disease Periodontaldisease is caused bya bacterialchal- lengethattriggers an inflammatoryreaction in a susceptible host. Alterations in the OPG/RANK/ RANKL complex, among other cytokines and lo- calfactors, have been linkedto an increase inthe periodontaldestruction,mediatedbytheincrease in RANKL production by inflammatory cells, mainly macrophages, and the decrease of OPG. Additionally,the periodontaltissue is affected by thefree radicalsthat burstfrom phagocytic cells, such as neutrophils and macrophages, which significantly damage the gingival tissue. Inviewofthese commonfactors andtargets, it is reasonableto expect an association between periodontal disease and levels of melatonin.46 Severalclinicalstudieshavedemonstratedit.3,4,47 These studies showedthat levels ofmelatonin in serum, saliva, gingivalcrevicularfluid orallthree are inversely associated with the severity of the disease,whichindicatesthatmelatoninmayhave a protective role against periodontal disease. Moreover, the effects of melatonin on the reduction of osteoclastogenesis, the capture of reactive oxygen species and their metabolites in the inflamed area, the increase in bone minera- E f f e c t s o f m e l a t o n i n o n b o n e