Nanog promotes osteogenic differentiation of the mouse mesenchymal cell line C3H10T1/2 by modulating bone morphogenetic protein(BMP) signaling.
Nanog promotes osteogenic differentiation of the mouse mesenchymal cell line C3H10T1/2 by modulating bone morphogenetic protein(BMP) signaling.
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Nanog 通过调节骨形态发生蛋白 (BMP) 信号传导促进小鼠间充质细胞系 C3H10T1/2 的成骨分化。
DOI：
10.1002/jcp.24116
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发表时间：
2013
期刊：
影响因子：
5.6
通讯作者：
and Hoshi K
中科院分区：
文献类型：
--
作者：
Ogasawara T;Ohba S;Yano F;Kawaguchi H;Chung UI;Saito T;Yonehara Y;Nakatsuka T;Mori Y;Takato T;and Hoshi K
如何维持干细胞的多能性以及转录因子在维持这一过程中的作用仍然是主要问题。在这项研究中，为了阐明干细胞多能性促进再生医学发展的潜在机制，我们检测了强制Nanog在间充质细胞中的表达，特别是成骨分化。用逆转录病毒载体将Nanog基因或对照绿色荧光蛋白(GFP)基因导入人骨髓间充质干细胞(HMSCs)或小鼠骨髓间充质细胞系C3H10T1/2细胞。短期强制表达Nanog基因对hMSCs和C3H10T1/2细胞的终末成骨分化几乎没有影响。为了确定其长期效应，我们建立了结构性表达Nanog的C3H10T1/2细胞。组成型Nanog表达可强烈诱导C3H10T1/2细胞向成骨方向分化。在细胞增殖方面，组成性Nanog表达仅抑制经rhBMP-2处理的C3H10T1/2细胞的增殖。此外，在没有rhBMP-2的情况下，Nanog还具有促进C3H10T1/2细胞增殖的作用。在表达Nanog的细胞中，骨钙素和ID-1基因的启动子活性均被激活。为了确定Nanog下游参与促进成骨分化的分子，我们进行了DNA微阵列分析，发现NFATc1是Nanog的下游效应分子之一。这些结果表明，Nanog可能通过基因组重编程过程在C3H10T1/2细胞中作为BMP信号的调制器发挥作用。J.细胞。物理。2013年，228：163-171。©2012 Wiley期刊，Inc.
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. J. Cell. Physiol. 228: 163–171, 2013. © 2012 Wiley Periodicals, Inc.