Melatonin protects gingival mesenchymal stem cells and promotes differentiation into osteoblasts

Abstract

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.

Regulation of Adipose-Derived Stem Cell Activity by Melatonin Receptors in Terms of Viability and Osteogenic Differentiation

“…Some studies have proven that melatonin promotes osteogenesis more efficiently in pathological cases than in osteoporotic defects [ 34 , 57 ] or periodontitis [ 58 ]. Data have shown that this process is related to the activation of the PI3K/AKT/mTOR pathway in stem cells after cell damage with, e.g., dexamethasone [ 57 ].…”

Antioxidant Materials in Oral and Maxillofacial Tissue Regeneration: A Narrative Review of the Literature

“…Melatonin is a human hormone with various functions in human health, such as keeping humans safe from certain cancers, delaying senescence, stimulating type I collagen fiber formation, and improving bone formation. Due to the increasing levels of free radicals during periodontal diseases, the level of antioxidants, such as melatonin, will be raised in the saliva to protect the oral cavity against oxidative stress and regenerate alveolar bone and collagen fibers [ 102 , 103 ]. In addition, melatonin increases collagen IIIα1, decorin, and IL10; It also decreases the matrix metalloproteinase 1 (MMP1)/tissue inhibitor metalloproteinase protein 1 (TIMP1) ratio, which is suitable for alveolar bone formation in the oral cavity.…”

“…In addition, melatonin increases collagen IIIα1, decorin, and IL10; It also decreases the matrix metalloproteinase 1 (MMP1)/tissue inhibitor metalloproteinase protein 1 (TIMP1) ratio, which is suitable for alveolar bone formation in the oral cavity. Regarding this, Sola et al [ 103 ] analyzed the antioxidant and osteogenic differentiation effects of melatonin on mesenchymal stem cells derived from the gingival mesenchymal stem cells (GMSCs). Results showed that melatonin protected GMSCs in a model of cellular damage (resulting from oxidative stress).…”