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机械应变诱导成骨分化:拉伸大鼠间充质干细胞中Cbfa1和Ets-1的表达

Mechanical strain induces osteogenic differentiation: Cbfa1 and Ets-1 expression in stretched rat mesenchymal stem cells.

作者信息

Qi M-C, Hu J, Zou S-J, Chen H-Q, Zhou H-X, Han L-C

机构信息

Laboratory of Biomedical Engineering, Basic Medicine and Forensic Medicine College, Sichuan University, Chengdu, China.

出版信息

Int J Oral Maxillofac Surg. 2008 May;37(5):453-8. doi: 10.1016/j.ijom.2007.12.008. Epub 2008 Feb 12.

DOI:10.1016/j.ijom.2007.12.008
PMID:18272346
Abstract

Distraction osteogenesis is an active process of bone regeneration under controlled mechanical stimulation. Osteogenic differentiation of mesenchymal stem cells (MSCs) is essential for bone formation during this process. Cbfa1 and Ets-1 (core binding factor alpha 1 and v-ets erythroblastosis virus E26 oncogene homolog 1) are transcription factors that play important roles in the differentiation of MSCs to osteoblasts. In order to mimic a single activation of a clinical distraction device, a short period of cyclic mechanical strain (40 min and 2,000 microstrains) was applied to rat MSCs. Cellular proliferation and alkaline phosphatase (ALP) activity were examined. The mRNA expression of Cbfa1 and Ets-1, as well as ALP, a specific osteoblast marker, was detected using real-time quantitative reverse transcription polymerase chain reaction. The results showed that mechanical strain can promote MSC proliferation, increase ALP activity and up-regulate the expression of Cbfa1 and Ets-1. A significant increase in Ets-1 expression was detected immediately after mechanical stimulation, but Cbfa1 expression was elevated later. The temporal expression pattern of ALP coincided perfectly with that of Cbfa1. Mechanical strain may act as a stimulator to induce differentiation of mesenchymal stem cells into osteoblasts, which is vital for bone formation in distraction osteogenesis.

摘要

牵张成骨是在可控机械刺激下的一种活跃的骨再生过程。在此过程中,间充质干细胞(MSCs)向成骨细胞的分化对于骨形成至关重要。Cbfa1和Ets-1(核心结合因子α1和v-ets成红细胞增多症病毒E26癌基因同源物1)是在MSCs向成骨细胞分化过程中发挥重要作用的转录因子。为模拟临床牵张装置的单次激活,对大鼠MSCs施加短时间的周期性机械应变(40分钟和2000微应变)。检测细胞增殖和碱性磷酸酶(ALP)活性。使用实时定量逆转录聚合酶链反应检测Cbfa1和Ets-1以及成骨细胞特异性标志物ALP的mRNA表达。结果表明,机械应变可促进MSCs增殖,增加ALP活性并上调Cbfa1和Ets-1的表达。机械刺激后立即检测到Ets-1表达显著增加,但Cbfa1表达随后升高。ALP的时间表达模式与Cbfa1完全一致。机械应变可能作为一种刺激物诱导间充质干细胞分化为成骨细胞,这对于牵张成骨中的骨形成至关重要。

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