Department of Plastic and Hand Surgery, Freiburg University Medical Center, Freiburg, Germany.
J Cell Biochem. 2013 Jul;114(7):1584-94. doi: 10.1002/jcb.24500.
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.
在骨工程中，最有前途的策略集中在提供足够的血管化来支持新形成的组织。在这方面，该领域的最新研究集中在研究骨形成细胞和内皮细胞之间的复杂相互作用。我们之前的工作已经证明，将人脐静脉内皮细胞（HUVEC）与原代人成骨细胞（hOB）直接共培养诱导 hOB 的成骨表型和存活。为了研究导致这种效应的机制，我们对 HUVEC 与 hOB 共培养后进行了微阵列基因表达谱分析。我们的数据揭示了深刻的转录组变化，这些变化依赖于这些细胞群体之间的直接细胞接触。使用 MetaCore™平台进行的途径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物显著上调。许多主要血管生成因子的上调证实了之前的观察结果，即 HUVEC 在与成骨细胞共培养时进入促血管生成状态。有趣的是，下调的转录本主要聚集在细胞周期相关过程周围。微阵列数据通过对选定基因的定量实时 RT-PCR 得到了证实。总之，这项研究为进一步研究内皮细胞和骨细胞之间的复杂相互作用提供了一个平台。
