Hypoxia inhibits the differentiation of mesenchymal stem cells into osteoblasts by activation of Notch signaling

被引：76
|
作者：
Xu, Ningru [1 ,2 ]
Liu, Hui
Qu, Feng [2 ]
Fan, Jun [2 ]
Mao, Kezheng [1 ]
Yin, Yi [1 ]
Liu, Jianheng [1 ]
Geng, Zhenying [2 ]
Wang, Yan [1 ]
机构：
[1] Chinese Peoples Liberat Army Gen Hosp, Dept Orthopaed, Beijing 100853, Peoples R China
[2] Nankai Univ, Coll Med, Tianjin 300071, Peoples R China
来源：
EXPERIMENTAL AND MOLECULAR PATHOLOGY | 2013年 / 94卷 / 01期
关键词：
Mesenchymal stem cell; Osteoblast; Hypoxia; Notch signaling; OXYGEN-TENSION; EXPRESSION; CBFA1;
D O I：
10.1016/j.yexmp.2012.08.003
中图分类号：
R36 [病理学];
学科分类号：
100104 ;
摘要：
Postnatal bone marrow contains mesenchymal stem cells (MSCs) that are osteoblast precursors with great therapeutic potential. The oxygen tension in bone marrow is about 1-7% pO2 which is much lower than that of the external environment. The effect of these hypoxic conditions on MSC differentiation is not fully understood. In this study, we show that hypoxia inhibits osteogenic differentiation of MSCs, and that this effect is associated with increased levels of Notch1 and increased activity of Notch signaling. Knockdown of Notch1 in MSCs by shRNA markedly rescues the impaired osteogenic differentiation of MSCs. Furthermore, Notch1 physiologically binds to Runx2 and inhibits its transcriptional activity. Thus, hypoxia inhibits MSC differentiation into osteoblasts by activating the Notch pathway. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码：33 / 39
页数：7
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