Melatonin protects gingival mesenchymal stem cells and promotes differentiation into osteoblasts

Melatonin (MEL) has antioxidant properties and participates in osteogenic differentiation. In periodontitis, in which increased oxidative stress and bone resorption are involved, mesenchymal stem cells derived from the gingiva (GMSCs) combined with MEL could be relevant for osteogenic regeneration. In this study, we studied the antioxidant and differentiating effect of MEL on an in vitro system of GMSCs. Primary culture of GMSCs from Wistar rats was developed to evaluate differentiation into osteoblasts with an appropriate medium with or without MEL. Marker genes of mesenchymal stem cells by real time‐polymerase chain reaction, clonogenic capacity, and cell migration after wound assay were used to characterize GMSCs as mesenchymal stem cells. Alkaline phosphatase activity and the alizarin red technique were used to evaluate osteogenic activity and differentiation. MEL increased alkaline phosphatase activity and alizarin red values, promoting osteogenic differentiation. Besides this, MEL protected GMSCs in a model of cellular damage related to oxidative stress, returning viability to baseline. MEL was more effective in promoting and protecting GMSCs by the production of osteogenic cells when oxidative stress is present. This evidence supports the use of MEL as a novel bone‐regenerative therapy in periodontal diseases. Significance statement This article provides new evidence on the protective role of melatonin as a possible therapeutic agent in gingival cells. In the present work, mesenchymal stem cells derived from the gingiva (GMSCs), which have been characterized as mesenchymal stem cells, are highly sensitive to cellular damage related to oxidative stress due to glutathione depletion. Melatonin was able to protect these cells from oxidative damage. Besides, remarkably, melatonin improved the osteogenic differentiation of GMSCs into osteoblasts. These molecular mechanisms open a new perspective to the use of melatonin together with GMSCs in a context of reproducibility, which could support future clinical interventions for regenerative periodontics.