The Effect of Antidepressants on Mesenchymal Stem Cell Differentiation

Abstract

BackgroundUse 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 dose-dependent effect on mesenchymal stem cell (MSC) differentiation, which may affect bone metabolism.MethodsHuman MSCs (hMSCs) were committed to differentiate when either adipogenic or osteogenic media was 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 MTT.ResultsWe 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.ConclusionsThis study showed 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, affected both osteoblastogenesis and adipogenesis, this inhibitory effect could be associated to the high affinity of fluoxetine to the serotonin transporter system.

Effects of different antidepressant classes on dental implant failure: A retrospective clinical study

“…Previous evidence showed that both serotonin and norepinephrine affect bone metabolism and turnover, as functional serotonin and norepinephrine transporters/receptors are present in peripheral bone cells 13‒20 . Serotonin may induce proliferation of osteoblasts, whereas SSRI may inhibit bone cell function via apoptosis and impede bone mineralization.…”

Post-SSRI Sexual Dysfunction: A Bioelectric Mechanism?

“…Importantly, however, the ion channel and gap junction networks that implement bioelectric control circuits are ubiquitous, being present and function across taxa, from bacterial biofilms to mammals. [41][42][43][44][45][46][47][48][49][50][51][52] Effects on cell migration, 53 proliferation, 54 migration/pathfinding, 55,56 and stem cell differentiation 57 have been observed after modulation of neurotransmitter pathways. Even the microbiome, with many known roles in regulating mood and functioning of many organ systems, has been affected by neurotransmitter signaling.…”

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

“…Some studies reported that FLX may exert a role as apoptosis inducer however antiapoptotic properties of FLX also were discussed [10][11][12]. Some studies expressed that FLX could prevent cell differentiation, on the other hand, there are some documents on differentiation process improvement by FLX [9,[13][14][15].…”

“…Studies revealed that serotonin plays a main role in cell differentiation and negatively affects bone proliferation and osteoblast differentiation. One study reported that the inhibitory effect of FLX on cell differentiation is independent of serotonin, but the other study indicated that this inhibition is related to the strong affinity of FLX to serotonin transporter system . According to the lack of clarification on FLX impact in cellular processes, more investigations are needed to elucidate the FLX properties on these cellular events.…”

“…Complicated interplays between various molecular factors such as bone morphogenic proteins, Wnt proteins, and several transcription factors regulate the differentiation process of mesenchymal stem cells. Any imbalance and change in the abovementioned regulation leads to alteration of differentiation process .…”