Cholesterol myristate suppresses the apoptosis of mesenchymal stem cells via upregulation of inhibitor of differentiation
Cholesterol myristate suppresses the apoptosis of mesenchymal stem cells via upregulation of inhibitor of differentiation
复制标题
肉豆蔻酸胆固醇通过上调分化抑制剂抑制间充质干细胞凋亡
DOI：
10.1016/j.steroids.2010.07.009
复制
发表时间：
2010-12-12
期刊：
影响因子：
2.7
通讯作者：
Hu, Zi-Chun
中科院分区：
文献类型：
--
作者：
Chen, Dong-Feng;Zhang, Hai-Ling;Hu, Zi-Chun
寻找抑制间充质干细胞(MSCs)凋亡的小分子有望成为干细胞治疗的新途径。我们最近发现骨形态发生蛋白4(BMP4)信号涉及胆固醇肉豆蔻酸盐对MSCs增殖的影响。本研究探讨肉豆蔻酸胆固醇对骨髓间充质干细胞凋亡及分化抑制因子(ID1)的影响。BMP4信号转导的靶基因。构建Id1启动子报告载体后，肉豆蔻酸胆固醇可提高Id1启动子的活性。然而，结构上相关的类固醇，如胆固醇、β-谷甾醇和胆固酮-3-酮，缺乏肉豆蔻酸盐，并不影响Id1启动子的活性，这表明肉豆蔻酸盐对这一作用是必不可少的。这种作用依赖于BMP信号。细胞凋亡分析表明，肉豆蔻酸胆固醇可抑制无血清诱导的MSCs的凋亡。肉豆蔻酸胆固醇促进无血清处理的MSCs Id1及其靶基因bclx/L的表达。此外，BMP拮抗剂Noggin降低了胆固醇肉豆蔻酸盐的抗细胞凋亡作用。因此，本研究旨在为肉豆蔻酸胆固醇通过上调Id1抑制MSCs的凋亡提供证据。这些发现可用于提高干细胞移植、骨髓移植、骨质疏松症等骨病的治疗和化疗中的MSCs存活率。(C)2010 Elsevier Inc.保留所有权利。
To identify small molecules that suppress the apoptosis of mesenchymal stem cells (MSCs) is promising for stem cell therapy. We recently showed that bone morphogenetic protein 4 (BMP4) signalling involves the effect of cholesterol myristate on the proliferation of MSCs. The present study evaluated the effects of cholesterol myristate on the apoptosis of MSCs and the inhibitor of differentiation (Id1). target gene of BMP4 signalling. MSCs transfected by the Id1 promoter reporter construct, cholesterol myristate increases the activity of Id1 promoter. However, structurally related steroids such as cholesterol, beta-sitosterol and cholesten-3-one, lack of the myristate, did not affect the activity of Id1 promoter, suggesting that myristate is essential for this effect. This effect depends on BMP signalling. Apoptosis analysis indicated that cholesterol myristate inhibited the apoptosis of MSCs induced by serum-free. Cholesterol myristate increases the expression of Id1 and its target gene bcl-x/l in MSCs treated with serum-free. Moreover, noggin, a BMP antagonist, reduced the anti-apoptotic effects of cholesterol myristate. Thus, this study aims to provide evidence that cholesterol myristate suppresses the apoptosis of MSCs via upregulation of Id1. These findings can be applied for improving MSCs survival in stem-cell transplantation, bone-marrow transplantation, treatment of bone diseases such as osteoporosis and chemotherapy. (C) 2010 Elsevier Inc. All rights reserved.