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Journal of Oral Science & Rehabilitation 13 Volume 2 | Issue 2/2016 lization through the increase in proliferation, dif- ferentiation and activity of osteoblasts, and col- lagen and BSP regulation, as already explained, together with its anti-fibrotic and anti-inflam- matory effects on gingival tissue by a reduction ofthematrixmetalloproteinase-1/tissueinhibitor ofmetalloproteinases-1 ratio, suggestthe possi- bility of using melatonin as a host-modulating agent inthetreatment and controlofperiodontal disease, improving the bone tissue conditions and the soft-tissue stability.48 The in vivo admi- nistration of local or systemic melatonin could, therefore,beindicatedinthesepatients,although no studies haveyet been performed inthis sense with validated methods. Melatonin and dental implants Dental implants are commonly used in current treatment oftooth loss. However,to avoid poten- tial early complications and implant failures,49, 50 bone healing must occurinthe properway. Bone remodeling around dental implants is highly in- fluenced by the implant surface characteristics and evolves as a balance between the activity of osteoblasts and osteoclasts.51, 52 Therefore, the use ofmelatonin as atopicalagentto induce bio- mimetic properties of the implant surface has emerged as a promising technique.53 Melatonin directly influences the osteoblast’s response to the implant surface and osseointegration. The addition of melatonin improves results for cell adhesion, proliferation and differentiation on dif- ferent titanium surface modifications at early time points, although longer culturing times seem to reduce those differences.54 These effects have been confirmed in vivo in several studies.55, 56 The effects around dental implants are similar to those that take place in bone repair. Bone repair consists, biologically, of three different stages: inflammatory, prolifera- tive and remodeling. Melatonin may play a role in these phases owing to its regulatory effects on inflammation, antioxidant properties, regu- lation of bone cells, and stimulation of collagen synthesis and deposition. Moreover, melatonin has been shownto increasethe numberofblood vessels, which is a prerequisite for the supply of mineral elements and the migration of angioge- nic and osteogenic cells. As a consequence, his- tological evaluation of the periimplant bone shows more trabecular bone, but less cortical bone and higher bone-to-implant contact in melatonin-treated sockets compared with con- trols.55 Therefore,theuseofmelatoninforosseo- integration might be of interest as a biomimetic agent.Moreover,ithasbeensuggestedtoinduce bone growth when applied in combination with bone grafts.56 However, its potential use in re- generating post-periimplantitis defects has not been studied yet. Conclusion Melatonin positive regulation of bone formation and homeostasis, in combination with the inhib- itory effects on bone resorption, highlights the potential use of melatonin as a marker of peri- odontal and periimplant bone-related diseases. Moreover, invitro and animalstudies are starting to show promising results on its use as a regen- erative agent, although no clinical studies have yet been performed. This new strategy may cre- ate possibilities for novel therapies in the treat- ment of periodontal disease or enhancing the outcomes of implant dentistry. Competing interests The authors declare that they have no conflict of interests related to this study. Acknowledgments The authors would like to thank Mr. Chris Jung for the original images presented in this review. MPM receivedfundingfromtheTalentia Fellow- ship Program (Regional Government of Andalu- sia, Spain). The authors have been partially sup- ported by Research Groups No. CTS-138 and No. CTS-583 (Regional Government of Andalu- sia) and by the Andalucía Talent Hub Fellowship Program (European Union’s Seventh Framework Programme, Marie Skłodowska-Curie actions, COFUND, grant agreement No. 291780; and Regional Government of Andalusia). E f f e c t s o f m e l a t o n i n o n b o n e