Rosiglitazone stimulates adipogenesis and decreases osteoblastogenesis in human mesenchymal stem cells
Rosiglitazone stimulates adipogenesis and decreases osteoblastogenesis in human mesenchymal stem cells
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DOI：
10.1007/bf03350807
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发表时间：
2007-10-01
影响因子：
5.4
通讯作者：
Serio, M.
中科院分区：
文献类型：
--
作者：
Benvenuti, S.;Cellai, I.;Serio, M.
噻唑烷二酮类药物 (TZD) 广泛用于治疗 2 型糖尿病。绝经后妇女使用此类药物会导致骨质流失增加和骨折发生率升高。在啮齿动物细胞模型中进行的体外研究表明，罗格列酮（RGZ）（TZD 之一）可抑制骨髓祖细胞中的成骨细胞生成并诱导脂肪生成。本研究的目的是首次利用人类细胞模型确定 RGZ 依赖性从成骨细胞生成向脂肪生成的转变。为此，对骨髓来源的间充质干细胞进行了表征并诱导其沿成骨和脂肪形成谱系分化。我们发现，通过脂滴的出现评估，暴露于 RGZ 会增强脂肪形成分化，并将分化从成骨表型转变为脂肪形成表型。因此，RGZ 显着增加了脂肪生成脂肪酸结合蛋白 4 的典型标志物的表达，而降低了成骨细胞生成标志物 Runx2 的表达。这是首次证明 RGZ 可以抵消成骨细胞生成并诱导人间充质干细胞优先分化为脂肪细胞。
Thiazolidinediones (TZD) are widely prescribed for the treatment of Type 2 diabetes. Increased loss of bone mass and a higher incidence of fractures have been associated with the use of this class of drugs in post-menopausal women. In vitro studies performed in rodent cell models indicated that rosiglitazone (RGZ), one of the TZD, inhibited osteoblastogenesis and induced adipogenesis in bone marrow progenitor cells. The objective of the present study was to determine for the first time the RGZ-dependent shift from osteoblastogenesis toward adipogenesis using a human cell model. To this purpose, bone marrow-derived mesenchymal stem cells were characterized and induced to differentiate along osteogenic and adipogenic lineages. We found that the exposure to RGZ potentiated adipogenic differentiation and shifted the differentiation toward an osteogenic phenotype into an adipogenic phenotype, as assessed by the appearance of lipid droplets. Accordingly, RGZ markedly increased the expression of the typical marker of adipogenesis fatty-acid binding protein 4, whereas it reduced the expression of Runx2, a marker of osteoblastogenesis. This is the first demonstration that RGZ counteracts osteoblastogenesis and induces a preferential differentiation into adipocytes in human mesenchymal stem cells.