Xue Ying, Xing Zhe, Bolstad Anne Isine, Van Dyke Thomas E, Mustafa Kamal
Department of Clinical Dentistry - Center for Clinical Dental Research, University of Bergen, Bergen - Norway.
Int J Artif Organs. 2013 Oct 3;36(9):650-62. doi: 10.5301/ijao.5000229. Epub 2013 Aug 2.
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.
体内血管生成与骨生成之间的复杂关系必须在骨组织工程构建物中得以重现，以确保形成功能性血管网络来支持成功的骨形成。尽管骨髓基质细胞（MSC）与内皮细胞（EC）之间的通讯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充分理解。本研究的目的是使用具有单通道平台系统的HumanWG-6 v3.0表达微珠芯片（Illumina，美国加利福尼亚州圣地亚哥）分析与MSC和EC之间细胞间通讯相关的全局基因表达。每个芯片包含来自人类基因的48,000多个探针。在直接接触模型中，将MSC与EC共培养5天和15天后，生成了MSC基因表达的全局图谱。该图谱用于确定功能过程和通路中的相对变化。将EC与MSC共培养上调了与血管生成相关的基因，如血管性血友病因子、血小板/内皮细胞黏附分子-1、钙黏蛋白5、血管生成素相关蛋白4和细胞表面抗原CD34，以及在骨生成中起重要作用的基因，如碱性磷酸酶、FK506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有显著影响，特别是对血管生成和骨生成的双向调节。此外，细胞-基质相互作用和TGF-β信号通路在EC诱导的MSC基因调控中起着关键作用。有必要对微阵列数据的功能相关性进行详细研究，以探索骨组织工程中重要的细胞和分子相互作用。
