Melatonin Ameliorates Experimental Periodontitis Through Modulation of Osteoblastic Activities

Objectives: The aim of this study was to evaluate in vivo and in vitro effects of melatonin on periodontitis by examining alveolar bone destruction in rat-model of experimental periodontitis along with its influence on osteoblastic activities.
Methods: Sprague-Dawley rats were separated into control (C), ligature (L), and ligature-melatonin (L-Mel) groups (n=5 per group). Ligature-induced experimental periodontitis in rats was established by having 3-O silk wrapped bilaterally around the cervical margins of the maxillary second molars. Ligature-melatonin groups were subdivided into two groups treated with 10 mg/kg or 100mg/kg through oral gavage for 14 days. After 14 days, the rats were sacrificed for Micro-CT and histological analysis, including CEJ-ABC distance, inflammatory cell infiltration, and immuno-histochemical staining of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL). MC3T3-E1 cells were treated with melatonin at concentrations of 12.5 - 200nM, and mineralization effects were examined through alkaline phosphatase (ALP) activity and Alizarin Red Staining (ARS).
Results: Systemic administration of melatonin in Sprague-Dawley rats induced with experimental periodontitis showed reduced alveolar bone destruction and decreased polymorphonuclear cells infiltration compared to rats with periodontitis not treated with melatonin. Melatonin showed no toxicity to MC3T3-E1 cells for concentrations up to 500nM. In addition, melatonin increased mineralization activity of MC3T3-E1 cells after differentiation in vitro with immuno-histochemical staining results which correspond to results in vivo.
Conclusions: Melatonin may have potential therapeutic effects on periodontitis through modulation of osteoblastic activities, and more studies should be conducted to further investigate its mechanism.