Increased extracellular matrix and proangiogenic factor transcription in endothelial cells after cocultivation with primary human osteoblasts
Increased extracellular matrix and proangiogenic factor transcription in endothelial cells after cocultivation with primary human osteoblasts
复制标题
DOI：
10.1002/jcb.24500
复制
发表时间：
2013-07-01
影响因子：
4
通讯作者：
Lampert, F.
中科院分区：
文献类型：
--
作者：
Simunovic, F.;Steiner, D.;Lampert, F.
骨工程中最有希望的策略集中在提供足够的血管来支持新形成的组织。在这种背景下，最近该领域的研究集中在研究骨形成和内皮细胞之间的复杂相互作用。我们以前的工作已经证明，人脐静脉内皮细胞(HUVECs)与原代人成骨细胞(HOBS)直接接触共培养可以诱导HOBS的成骨表型和存活。为了研究导致这种效应的机制，我们在HUVEC与HOBS共培养后进行了微阵列基因表达谱分析。我们的数据揭示了依赖于这些细胞群体之间的直接细胞接触的深刻的转录变化。利用MetaCore平台进行的通路分析和文献研究表明，与细胞外基质和细胞-基质相互作用相关的转录产物显著上调。一些主要的血管生成因子的上调证实了先前的观察结果，即人脐静脉内皮细胞与成骨细胞共培养后进入促血管生成状态。有趣的是，下调的转录本主要围绕细胞周期相关的过程聚集。所选基因的实时定量RT-PCR验证了微阵列数据的正确性。总之，这项研究为进一步研究内皮细胞和成骨细胞之间的复杂相互作用提供了一个平台。J.细胞。生物化学。2013年，114：15841594。(C)2013年威利期刊公司。
The most promising strategies in bone engineering have concentrated on providing sufficient vascularization to support the newly forming tissue. In this context, recent research in the field has focused on studying the complex interactions between bone forming and endothelial cells. Our previous work has demonstrated that direct contact cocultivation of human umbilical vein endothelial cells (HUVECs) with primary human osteoblasts (hOBs) induces the osteogenic phenotype and survival of hOBs. In order to investigate the mechanisms that lead to this effect, we performed microarray gene expression profiling on HUVECs following cocultivation with hOBs. Our data reveal profound transcriptomic changes that are dependent on direct cell contact between these cell populations. Pathway analysis using the MetaCore platform and literature research suggested a striking upregulation of transcripts related to extracellular matrix and cell-matrix interactions. Upregulation of a number of major angiogenetic factors confirms previous observations that HUVECs enter a proangiogenic state upon cocultivation with osteoblasts. Interestingly, the downregulated transcripts clustered predominantly around cell cycle-related processes. The microarray data were confirmed by quantitative real-time RT-PCR on selected genes. Taken together, this study provides a platform for further inquiries in complex interactions between endothelial cells and osteoblasts. J. Cell. Biochem. 114: 15841594, 2013. (c) 2013 Wiley Periodicals, Inc.