Co-culture of human bone marrow stromal cells with endothelial cells alters gene expression profiles.

Co-culture of human bone marrow stromal cells with endothelial cells alters gene expression profiles.
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DOI:
10.5301/ijao.5000229
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发表时间:
2013-10-03
期刊:
The International journal of artificial organs
影响因子:
--
通讯作者:
Mustafa K
Mustafa K
中科院分区:
其他
文献类型:
--
作者:
Xue Y;Xing Z;Bolstad AI;Van Dyke TE;Mustafa K

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体内血管生成和成骨之间的复杂关系必须在骨组织工程构建体中复制,以确保功能性血管网络的形成,以支持成功的骨形成。虽然骨髓基质细胞(MSC)和内皮细胞(EC)之间的通信被认为是骨再生中最重要的细胞相互作用之一,但这一生物学过程的潜在机制尚未得到很好的理解。本研究的目的是使用具有单通道平台系统的HumanWG-6 v3.0表达BeadChips(Illumina,San Diego,CA,USA)分析与MSC和EC之间的细胞间通讯相关的全局基因表达。每个阵列包含超过48,000个来自人类基因的探针。在直接接触模型中,MSC与EC共培养5天和15天后生成MSC基因表达的全局图。该图谱用于确定功能过程和途径的相对改变。EC与MSC共培养上调血管生成相关基因如von Willebrand因子、血小板/内皮细胞粘附分子-1、钙粘蛋白5、血管生成素相关蛋白4和细胞表面抗原CD 34,以及在成骨中起重要作用的基因如碱性磷酸酶、FK 506结合蛋白5和骨形态发生蛋白。这些发现清楚地表明EC对MSC具有显著影响,特别是对血管生成和成骨的双向调节。此外,细胞-基质相互作用和TGF-β信号通路在MSC中内皮细胞诱导的基因调控中起关键作用。一个详细的功能相关的芯片数据的研究是必要的,以探索在骨组织工程的重要性细胞和分子的相互作用。
The intricate relationship between angiogenesis and osteogenesis in vivo must be replicated in bone tissue engineering constructs to ensure the formation of a functional vascular network to support successful bone formation. Although communication between bone marrow stromal cells (MSC) and endothelial cells (EC) is recognized as one of the most important cellular interactions in bone regeneration, the underlying mechanisms of this biological process are not well understood. The purpose of this study was to analyze global gene expression associated with intercellular communication between MSC and EC using HumanWG-6 v3.0 expression BeadChips with a one-channel platform system (Illumina, San Diego, CA, USA). Each array contains more than 48,000 probes derived from human genes. A global map of MSC gene expression was generated following co-culture of MSC with EC for 5 and 15 days, in a direct-contact model. The map was used to determine relative alterations in functional processes and pathways. Co-culturing EC with MSC up-regulated genes related to angiogenesis as von Willebrand factor, platelet/endothelial cell adhesion molecule-1, cadherin 5, angiopoietin-related protein 4, and cell surface antigen CD34, and genes playing important roles in osteogenesis as alkaline phosphatase, FK506 binding protein 5, and bone morphogenetic protein. These findings clearly demonstrated that EC had a significant impact on MSC, particularly the bidirectional regulation of angiogenesis and osteogenesis. Moreover, cell-matrix interactions and TGF-β signal pathways were implicated for a crucial role in endothelial, cell-induced gene regulation in MSCs. A detailed study of the functional correlates of the microarray data is warranted to explore cellular and molecular interactions of importance in bone tissue engineering.
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