Effects of melatonin on the proliferation and differentiation of rat adipose-derived stem cells

Abstract

Background:Osteogenesis driven by adipose-derived stem cells (ADSCs) is regulated by physiological and pathological factors. Accumulating evidence from in vitro and in vivo experiments suggests that melatonin may have an influence on bone formation. However, little is known about the effects of melatonin on osteogenesis, which thus remains to be elucidated. This study was performed to determine whether melatonin at physiological concentrations (0.01-10 nM) could affect the in vitro proliferation and osteogenic differentiation of rat ADSCs.Materials and Methods:ADSCs were isolated from the fat of adult rats. After cell expansion in culture media and through three passages, osteogenesis was induced in a monolayer culture using osteogenic medium with or without melatonin at physiological concentrations (0.01-10 nM). After four weeks, the cultures were examined for mineralization by Alizarin Red S and von Kossa staining and for alkaline phosphatase (ALP) activity using an ALP kit. Cell viability and apoptosis were also assayed by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTT) assay and flow cytometry, respectively.Results:The results indicated that at physiological concentrations, melatonin suppressed proliferation and differentiation of ADSCs. These data indicate that ADSCs exposed to melatonin, had a lower ALP activity in contrast to the cells exposed to osteogenic medium alone. Similarly, mineral deposition (calcium level) also decreased in the presence of melatonin. Flow cytometry confirmed that cell growth had decreased and that the numbers of apoptotic cells had increased.Conclusion:These results suggest that the physiological concentration of melatonin has a negative effect on ADSC osteogenesis.

Melatonin promotes triacylglycerol accumulation via MT2 receptor during differentiation in bovine intramuscular preadipocytes

“…Previous studies demonstrated that the role of melatonin in the regulation of cell proliferation dependents on concentration and exposure time as well as cell type and species 39 , 40 . For example, melatonin has no significant effect on bovine granulosa cell proliferation 41 but significantly promotes the proliferation of porcine granulosa cells 42 .…”

“…In mammals, numerous physiological roles of melatonin are mediated via activation of two high-affinity G protein-coupled receptors, MT1 and MT2 28 , 29 . MT1 and MT2 mediate the physiological role of melatonin in a manner dependent on melatonin concentration and exposure time, as well as cell type 39 , 40 . We found co-expression of MT1 and MT2 in BIPs and reported that MT2 expression exhibited significant differences during BIPs differentiation.…”

Scientific Basis for the Potential Use of Melatonin in Bone Diseases: Osteoporosis and Adolescent Idiopathic Scoliosis

“…The age-related decrease of melatonin production could shift the bone marrow cells differentiation from osteoblastic differentiation toward an adipocytic line of cell, which could explain the development of osteoporosis during aging [ 37 ]. Melatonin also promotes the osteogenic differentiation of bone marrow stem cells whereas it has negative effects on differentiation of adipose-derived stem cells [ 38 , 39 ].…”

Evaluation of autologous adipose‐derived stem cells vs. fractional carbon dioxide laser in the treatment of post acne scars: a split‐face study

“…17 These features make them of great potential in the management of a large number of diseases, especially degenerative conditions, 18 including skin exposed to injury or disease. Functional stem cells are present throughout all layers of the skin, they enable skin regeneration through their physical and chemical signals, 19 yet it is somehow limited.…”