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ePaper created 2016-06-09, 15:16:05 | version 1.38.0
Journal of Oral Science & Rehabilitation 11 Volume 2 | Issue 2/2016 MELATONIN Influence on bone homeostasis Direct effects Indirect effects OSTEOBLASTS OSTEOCLASTS Increases secretion of Type I collagen Increases expression of BSP and other markers (ALP, OC) Downregulation of resorptive activity by modulating the balance of RANK/RANKL/OPG Scavenging of free radicals secreted by osteoclasts in the resorptive process OTHER CELLS Fibroblasts Increases proliferation and collagen synthesis Immune cells Stimulates secretion of cytokines (IL-2, IL-6) IMMUNE SYSTEM FREE RADICALS P/Ca2+ BALANCE Estrogen/Calcitonin PTH/Glucocorticoids Twist-1 and -2 gene expression Decreases inflammatory acute reaction Scavenger + Antioxidant Fig. 2 Effects of melatonin on bone. ALP: alkaline phosphatase; OC: osteocalcin. mechanisms underlying this resorption involves the protective superoxide-scavenging enzyme superoxide dismutase. Melatonin is a significant free-radical scavenger and antioxidant at both physiological and pharmacological concentra- tions.6 Beside its ability to directly neutralize a number of free radicals and reactive oxygen and nitrogen species, melatonin stimulates several antioxidativeenzymes,19,25 limitingthe resorptive osteoclast activity. Indirect effects on bone I . R e l a t i o n s h i p w i t h h o r m o n e s a n d g e n e s i n v o l v e d i n b o n e t u r n o v e r Melatonin is an important modulator of calcium and phosphorus metabolism.26 In addition to its direct actions on cells that modulate bone ho- meostasis, melatonin may exert its effects indi- rectly on the bone system by influencing the activity of important regulators of the phos- phorus–calcium balance and bone metabolism. Manystudies have indicatedthat melatonin may influencethereleaseofseveralfactorsthataffect bone, such as calcitonin,27 corticosterone,28 growth factors29 and immunological factors.30 – Calcitonin,togetherwith bisphosphonates and estrogens, is an important regulator of the apoptosis ofosteoclasts. It is a powerfulinhib- itor of osteoclastic resorptive activity by pro- moting the reduction of contact between os- teoclasts and the bone surface, altering the morphologyofosteoclastsanddecreasingtheir mobility. Melatonin increases secretion of cal- citonininrats,andthismayinhibitboneresorp- tion.31 – PTH increases the expression of RANKL and decreases the expression of OPG. Melatonin decreases the levels of PTH, and this may, in- directly, generate an increase in bone mineral- ization.32 Fig. 2 E f f e c t s o f m e l a t o n i n o n b o n e