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        The Effect of Antidepressants on Mesenchymal Stem Cell Differentiation

        Jeffrey S. Kruk,Sandra Bermeo,Kristen K. Skarratt,Stephen J. Fuller,Gustavo Duque 대한골대사학회 2018 대한골대사학회지 Vol.25 No.1

        Background: Use of antidepressant medications has been linked to detrimental impacts on bone mineral density and osteoporosis; however, the cellular basis behind these observations remains poorly understood. The effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. In this study, we hypothesized that antidepressants have a class- and dosedependent effect on mesenchymal stem cell (MSC) differentiation, which may affect bone metabolism. Methods: Human MSCs (hMSCs) were committed to differentiate when either adipogenic or osteogenic media is added, supplemented with five increasing concentrations of amitriptyline (0.001-10 μM), venlafaxine (0.01-25 μM), or fluoxetine (0.001-10 μM). Alizarin red staining (mineralization), alkaline phosphatase (osteoblastogenesis), and oil red O (adipogenesis) assays were performed at timed intervals. In addition, cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl- 2H-tetrazolium bromide-formazan assay. Results: We found that fluoxetine had a significant inhibitory effect on mineralization. Furthermore, adipogenic differentiation of hMSC was affected by the addition of amitriptyline, venlafaxine, and fluoxetine to the media. Finally, none of the tested medications significantly affected cell survival. Conclusions: This study shows a divergent effect of three antidepressants on hMSC differentiation, which appears to be independent of class and dose. As fluoxetine and amitriptyline, but not venlafaxine, were affected both osteoblastogenesis and adipogenesis, this inhibitory effect could be associated to the high affinity of fluoxetine to the serotonin transporter system.

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