The effects of fluoxetine on the human adipose-derived stem cell proliferation and differentiation

Fluoxetine is one of the most commonly used antidepressants. Fluoxetine could prevent the mesenchymal stem cell differentiation in lung fetus of rat. Moreover, the mesenchymal stem cells are also present in adult tissues. Therefore, in the current study, we aimed to investigate the effects of fluoxetine (FLX) on both proliferation and adipogenic/osteogenic differentiation of human adipose-derived stem cells (ADSCs). After culturing of human ADSCs, these cells were treated with two concentrations of FLX (10 and 20 mu m). Then, cells were differentiated by adding osteogenic and adipogenic media. The effect of FLX on human ADSCs proliferation was evaluated by MTT assay. Fluoxetine role on adipogenic and osteogenic differentiation of human ADSCs was analyzed by oil red and alizarin red staining and RT-PCR reaction. According to MTT assay, FLX showed a time- and concentration-dependent proliferation response and eventually decreased human ADSCs proliferation. RT-PCR analysis indicated that FLX significantly diminished the expression of osteogenesis-related genes such as RUNX2 and alkaline phosphatase (ALP). Data also revealed a significant reduction in the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) and fatty acid-binding protein (FABP) (specific genes of adipogenic lineage). In addition, FLX decreased mineralized matrix and the amount of lipid droplets in human ADSCs by staining methods. Our observation demonstrated that the effects of FLX may be time-dependent. This drug possesses an increasing phase in proliferation and survival of human ADSCs (first 24 h) following a decreasing phase (after 48 h). Moreover, FLX could attenuate both osteogenic and adipogenic differentiation of human ADSCs.