Cytoskeletal proteins and stem cell markers gene expression in human bone marrow mesenchymal stromal cells after different periods of simulated microgravity

Cytoskeletal proteins and stem cell markers gene expression in human bone marrow mesenchymal stromal cells after different periods of simulated microgravity
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DOI:
10.1016/j.actaastro.2011.07.028
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发表时间:
2012-01-01
期刊:
影响因子:
3.5
通讯作者:
Buravkova, L. B.
Buravkova, L. B.
中科院分区:
工程技术3区
文献类型:
--
作者:
Gershovich, P. M.;Gershovich, J. G.;Buravkova, L. B.

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间充质干细胞(MSCs)存在于产前和产后人类发育的多种组织中。在成年生物体中,它们普遍存在于骨髓中,并被认为与太空飞行引起的骨质减少有关。我们研究了随机定位机提供的模拟微重力(SMG)不同条件下人骨髓间充质干细胞中各种基因的表达。模拟微重力诱导肌动蛋白细胞骨架相关基因表达水平的短暂变化,特别是在SMG 48小时后。然而,暴露在SMG中120小时后,发现基因表达水平部分恢复(相对于对照组)。bmMSCs在SMG中培养24小时后,在静态状态下重新适应24小时,也得到了类似的结果。对84个与干细胞鉴定、生长和分化相关的基因进行分析,发现SMG中有9个基因在48 h后表达略有变化。在模拟微重力120小时后,“干细胞标记物”的基因表达发生了更明显的变化。84个基因中,30个基因上调,24个基因下调。最后,长期(10-20天)模拟微重力诱导MSCs成骨,MSCs主要成骨分化标志物(ALPL、OMD)和主转录成骨因子(Runx2)基因表达下调。因此,我们的研究表明,与肌动蛋白细胞骨架和干细胞标记相关的一些基因表达水平的变化可能是前体细胞适应微重力条件的机制之一。这些结果可以阐明SMG减少骨髓间充质干细胞成骨分化的基因组机制。(C) 2011 Elsevier Ltd.版权所有。
Mesenchymal stem (stromal) cells (MSCs) are present in a variety of tissues during prenatal and postnatal human development. In adult organism, they are prevalent in bone marrow and supposed to be involved in space-flight induced osteopenia. We studied expression of various genes in human bone marrow MSCs after different terms of simulated microgravity (SMG) provided by Random Positioning Machine. Simulated microgravity induced transient changes in expression level of genes associated with actin cytoskeleton, especially after 48 h of SMG. However, after 120 h exposure in SMG partial restoration of gene expression levels (relative to the control) was found. Similar results were obtained with bmMSCs subjected to 24 h readaptation in static state after 24 h in SMG. Analysis of 84 genes related to identification, growth and differentiation of stem cells revealed that expression of nine genes was changed slightly after 48 h in SMG. More pronounced changes in gene expression of "stem cells markers" were observed after 120 h of simulated microgravity. Among 84 investigated genes, 30 were up-regulated and 24 were down-regulated. Finally, MSCs osteogenesis induced by long-term (10-20 days) simulation of microgravity was accompanied by down-regulation of gene expression of the main osteogenic differentiation markers (ALPL, OMD) and master transcription osteogenic factor of MSCs (Runx2). Thus, our study demonstrated that changes in expression level of some genes associated with actin cytoskeleton and stem cell markers are supposed to be one of the mechanisms, which contribute to precursor's cellular adaptation to the microgravity conditions. These results can clarify genomic mechanisms through which SMG reduces osteogenic differentiation of bmMSCs. (C) 2011 Elsevier Ltd. All rights reserved.