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

Mechanical strain induces osteogenic differentiation: Cbfa1 and Ets-1 expression in stretched rat mesenchymal stem cells
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DOI:
10.1016/j.ijom.2007.12.008
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发表时间:
2008-05-01
影响因子:
2.4
通讯作者:
Han, L. -C.
Han, L. -C.
中科院分区:
医学3区
文献类型:
--
作者:
Qi, M. -C.;Hu, J.;Han, L. -C.

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牵张成骨是在受控机械刺激下骨再生的活跃过程。在这一过程中,间充质干细胞(MSCs)的成骨分化是骨形成的关键。Cbfa1和Ets-1(核心结合因子α1和v-ETS红母细胞增生症病毒E26癌基因同源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。为了模拟临床牵张装置的单次激活,对大鼠骨髓间充质干细胞施加了短期循环机械应变(40min和2000微应变)。检测细胞增殖和碱性磷酸酶(ALP)活性。实时定量逆转录聚合酶链式反应检测Cbfa1、Ets-1及成骨细胞特异性标志物碱性磷酸酶(ALP)的表达。结果表明,机械应变可促进MSC增殖,提高ALP活性,上调Cbfa1和Ets-1的表达。机械刺激后即刻Ets-1的表达显著增加,而Cbfa1的表达随后升高。ALP和Cbfa1的时间表达模式完全一致。机械应变可能作为一种刺激因子,诱导间充质干细胞分化为成骨细胞,这对牵张成骨过程中的骨形成是至关重要的。
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 2000 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.