The Effects of Fluoxetine on the Human Mesenchymal Stem Cell Proliferation and Differentiation

Background and Aim: Fluoxetine is one of the most commonly usedantidepressants. Fluoxetine could prevent the mesenchymal stem cellsdifferentiation in lung fetus of the rat. Moreover, the mesenchymal stemcells are also present in adult tissues. Therefore, in the current study, weaimed to investigate the effects of fluoxetine on both proliferation andadipogenic/osteogenic differentiation of human adipose tissue-derivedadult mesenchymal stem cells (ADSCs).Methods: After culturing of human ADSCs, these cells were treatedwith two concentrations of fluoxetine (10 and 20 μM). Then, cells weredifferentiated by adding osteogenic and adipogenic media. The effect offluoxetine on human ADSCs proliferation was evaluated by MTT assay.Fluoxetine role on the adipogenic and osteogenic differentiation ofhuman ADSCs was analyzed by oil red and alizarin red staining andRT-PCR reaction.Results: According to MTT assay, fluoxetine showed a time andconcentration-dependent proliferation response and eventuallydecreased human ADSCs proliferation. RT-PCR analysis indicated thatfluoxetine significantly diminished the expression of osteogenesis-relatedgenes such as RUNX2 and ALP. Data also revealed a significant reductionin the expression of PPARγ and FABP (specific genes of adipogeniclineage). In addition, fluoxetine decreased mineralized matrix and thenumber of lipid droplets in human ADSCs by staining methods.Conclusion: Our observation demonstrated that the effects of fluoxetinemay be time dependent. This drug possesses an increasing phase inthe proliferation and survival of human ADSCs (first 24 h) following adecreasing phase (after 48 h). Moreover, fluoxetine could attenuate bothosteogenic and adipogenic differentiation of human ADSCs.

کلیدواژه ها:

Fluoxetine ، Human adipose tissue-derived adult mesenchymal stem cells (ADSCs) ، Proliferation ، Osteogenic differentiation ، Adipogenic differentiation