BACKGROUND: Use of antidepressant medications has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. 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 hypothesise that anti-depressants have a class- and dose-dependent effect on mesenchymal stem cells (MSCs) differentiation, which may affect bone metabolism.
MATERIALS AND METHODS: Human mesenchymal stem cells (MSCs) were plated at a density of 5 x 105 cells/well in 100cm2 dishes containing MSC growth media. After confluence, cells were committed to differentiate adding either adipogenic or osteogenic media supplemented with five increasing concentrations of fluoxetine (0.001-10M), venlafaxine (0.01-25M) or amitriptyline (0.001-10M). Untreated differentiating MSCs were used as control. Alkaline phosphatase (osteoblastogenesis), oil red O (adipogenesis), and Alizarin red staining (mineralisation) were performed at timed intervals (weeks 1 and 2). Additionally, cell viability was assessed using MTT Formazan assay.
RESULTS: We found that osteoblast differentiation was not affected by any of the tested drugs. Amitriptyline and fluoxetine have a significant and dose-dependent inhibitory effect on mineralisation. Furthermore, adipogenic differentiation of MSCs was affected by addition of amitriptyline and venlafaxine to the media. Finally, none of the tested medications affected cell survival.
CONCLUSIONS: This study shows a divergent effect of three anti-depressants on MSCs differentiation, which appears to be independent of class and dose. Since amitriptyline was the only drug to affect both osteoblastogenesis and adipogenesis, this inhibitory effect should be independent of the serotonin transporter system. Whether anti-depressants induce changes in MSC differentiation in vivo remains to be tested.