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首页> 外文期刊>Journal of Cellular Physiology >Nanog promotes osteogenic differentiation of the mouse mesenchymal cell line C3H10T1/2 by modulating bone morphogenetic protein (BMP) signaling
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Nanog promotes osteogenic differentiation of the mouse mesenchymal cell line C3H10T1/2 by modulating bone morphogenetic protein (BMP) signaling

机译:Nanog促进成骨分化的小鼠间充质细胞线C3H10T1/2调节骨形成蛋白(BMP)信号

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How the pluripotency of stem cells is maintained and the role of transcription factors in this maintenance remain major questions. In the present study, in order to clarify the mechanism underlying the pluripotency of stem cells for the advancement of regenerative medicine, we examined the effect of forced Nanog expression in mesenchymal cells, with a particular focus on osteogenic differentiation. The human mesenchymal stromal cells (hMSCs) or mouse mesenchymal cell line C3H10T1/2 cells were transduced with the Nanog gene or control green fluorescent protein (GFP) gene by using retrovirus vectors. Short-term, forced Nanog gene expression had few effects on the terminal osteogenic differentiation of either hMSCs or C3H10T1/2 cells. To determine its long-term effects, we established C3H10T1/2 cells expressing Nanog constitutively. Constitutive Nanog expression strongly induced osteogenic differentiation of C3H10T1/2 cells. In regard to cell proliferation, constitutive Nanog expression only repressed the proliferation of the cells treated with rhBMP-2. Moreover, Nanog also had the potential to promote the proliferation of C3H10T1/2 cells in the absence of rhBMP-2. Constitutive Nanog expression enhanced phosphorylation of Smad1/5/8 and suppressed Cdk4 and cyclinD1. The promoter activities of both the osteocalcin and Id-1 genes were activated in cells expressing Nanog constitutively. To identify downstream molecules of Nanog involved in the promotion of osteogenic differentiation, we performed a DNA microarray analysis and discovered that NFATc1 was one of the downstream effectors of Nanog. These results indicate that Nanog functions as a modulator of BMP signaling in C3H10T1/2 cells probably through a genome reprogramming process.
机译:干细胞的多能性是如何维护的和转录因子的作用维护仍然是主要问题。本研究,以阐明机制潜在的多能性干细胞再生医学的发展,我们检查迫使Nanog表达的影响间充质细胞,尤其关注成骨分化。间充质细胞基质细胞(hMSCs)或老鼠行C3H10T1/2细胞转导的Nanog绿色荧光蛋白基因或控制用逆转录病毒载体(GFP)基因。短期,强迫Nanog基因表达几乎没有对终端成骨的影响hMSCs或C3H10T1/2分化细胞。建立C3H10T1/2细胞表达Nanog结构上。强烈诱导成骨分化C3H10T1/2细胞。本构Nanog表达式只有压抑增殖的细胞rhBMP-2对待。此外,Nanog也有提升的潜力C3H10T1/2细胞的扩散缺乏rhBMP-2。增强的磷酸化Smad1/5/8和压制到和cyclinD1。骨钙素和活动符合基因激活细胞内表达Nanog吗结构上。Nanog参与促进成骨分化,我们进行了DNA微阵列分析和发现NFATc1就是其中之一Nanog的下游效应器。表明Nanog调制器的功能C3H10T1/2细胞BMP信号可能通过一个基因组重组的过程。

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