Maria Cecilia Hospital, GVM Care & Research, via Corriera 1, 48033, Cotignola, Ravenna, Italy; Department of Biomedical Sciences, University of Padova, via G. Colombo 3, 35100, Padova, Italy.
Plastic Clinic Surgery, University of Padova, via Giustiniani 2, 35100, Padova, Italy.
Biomed Pharmacother. 2019 Jun;114:108853. doi: 10.1016/j.biopha.2019.108853. Epub 2019 Apr 12.
It is known that users of psychotropic drugs often have weight gain, adverse effects on bone mineral density and osteoporosis, but the molecular basis for these side effects is poorly understood. The aim of this study is to evaluate the effects in vitro of duloxetine (a serotonin and norepinephrine reuptake inhibitor) and fluoxetine (a selective serotonin reuptake inhibitor) on the physiology of human adult stem cells. Adipose-derived stem cells (ADSCs) were isolated and characterized investigating phenotype morphology, expression and frequency of surface markers. Then, a non-toxic concentration of duloxetine and fluoxetine was selected to treat cells during adipogenic and osteogenic differentiation. Stemness properties and the differentiation potential of drug-treated cells were investigated by the quantification of adipogenic and osteogenic markers gene expression and histological staining. The collected data showed that the administration of a daily non-toxic dose of duloxetine and fluoxetine has not directly influenced ADSCs proliferation and their stemness properties. The treatment with duloxetine or fluoxetine did not lead to morphological alterations during adipogenic or osteogenic commitment. However, treatments with the antidepressant showed a slight difference in adipogenic gene expression timing. Furthermore, duloxetine treatment caused an advance in gene expression of early and late osteogenic markers. Fluoxetine instead caused an increase in expression of osteogenic genes compared to untreated cells. In contrast, in pre-differentiated cells, the daily treatment with duloxetine or fluoxetine did not alter the expression profile of adipogenic and osteogenic differentiation. In conclusion, a non-toxic concentration of duloxetine and fluoxetine does not alter the stemness properties of ADSCs and does not prevent the commitment of pre-differentiated ADSCs in adipocytes or osteocyte. Probably, the weight gain and osteoporotic effects associated with the use of psychotropic drugs could be closely related to the direct action of serotonin.
已知精神药物使用者常伴有体重增加、骨密度不良和骨质疏松等副作用，但这些副作用的分子基础仍知之甚少。本研究旨在评估度洛西汀（一种 5-羟色胺和去甲肾上腺素再摄取抑制剂）和氟西汀（一种选择性 5-羟色胺再摄取抑制剂）对人成体干细胞生理学的体外影响。脂肪来源的干细胞（ADSCs）被分离并进行特征分析，包括表型形态、表面标志物的表达和频率。然后，选择度洛西汀和氟西汀的无毒浓度在成脂和成骨分化过程中处理细胞。通过定量分析成脂和成骨标志物基因表达和组织学染色，研究药物处理细胞的干性特征和分化潜能。收集的数据表明，每日给予无毒剂量的度洛西汀和氟西汀不会直接影响 ADSCs 的增殖及其干性特征。度洛西汀或氟西汀的治疗并未导致成脂或成骨分化过程中的形态改变。然而，抗抑郁药的治疗在成脂基因表达的时间上显示出轻微的差异。此外，度洛西汀处理导致早期和晚期成骨标志物的基因表达提前。相比之下，氟西汀处理导致成骨基因的表达相对于未处理的细胞增加。相比之下，在预分化细胞中，每日给予度洛西汀或氟西汀不会改变成脂和成骨分化的基因表达谱。总之，无毒浓度的度洛西汀和氟西汀不会改变 ADSCs 的干性特征，也不会阻止预分化的 ADSCs 向脂肪细胞或成骨细胞分化。可能与使用精神药物相关的体重增加和骨质疏松作用与 5-羟色胺的直接作用密切相关。
