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富含钴铬的培养基可改善受剪应力的内皮细胞性能。

Cobalt-chromium-enriched medium ameliorates shear-stressed endothelial cell performance.

机构信息

Department of Chemistry and Biochemistry, Bioscience Institute, Sao Paulo State University, UNESP, Campus Botucatu, Botucatu, São Paulo, Brazil.

Department of Chemistry and Biochemistry, Bioscience Institute, Sao Paulo State University, UNESP, Campus Botucatu, Botucatu, São Paulo, Brazil; Electron Microscopy Center, IBB, UNESP, Botucatu, SP, Brazil.

出版信息

J Trace Elem Med Biol. 2019 Jul;54:163-171. doi: 10.1016/j.jtemb.2019.04.012. Epub 2019 Apr 24.

Abstract

Angiogenesis is a relevant mechanism to be considered for the success of bone healing, even considering endosseous implantable devices, providing adequate delivery of substances necessaries for the cell viability and bone de novo deposition. Within of the repertory of metal-based implantable alloys, cobalt-chromium (CoCr) has emerged with very interesting properties for biomedical applications. Additionally, we have shown that released molecules from implants devices are able to modulate cells away and because that we hypothesized these released molecules might act on endothelial cells. In order to better address this issue, we investigated the effect of Co-Cr-enriched medium on endothelial cells (HUVECs), considering a biological model subjecting those cells to shear-stress to partially mimic the physiological environment and further allow investigating intracellular pathways responsible to drive cytoskeletal rearrangement, cell viability and extracellular matrix (ECM) remodeling processes. Considering the analysis of the metalloproteinases (MMPs) activities, our data indicates an intense ECM remodeling in response to CoCr-enriched medium suggesting some role on angiogenesis once ECM remodeling is prerequisite to cell growth. This was better addressed by revealing its involvement on modifying both mRNA expression and protein levels of members of the MAPK family. Additionally, the expression of CDK4 gene was modulated within the cell response to Co-Cr-enriched medium, while the modulation in the expression of P15 and P21 indicates an important regulatory mechanism required. Overall, our results demonstrate that trace of CoCr elements triggers decisive intracellular signaling in shear-stressed endothelial cells, suggesting influence on angiogenesis-related mechanism and they bring novel insights to explain the biological activity of CoCr as it has been emerged as interesting biomedical materials within the medical and dentistry fields.

摘要

血管生成是骨愈合成功的一个相关机制,即使考虑到骨内可植入装置,也能为细胞活力和新骨沉积所需的物质提供足够的输送。在基于金属的可植入合金中,钴铬(CoCr)因其在生物医学应用中的非常有趣的特性而脱颖而出。此外,我们已经表明,来自植入设备的释放分子能够调节细胞,因此我们假设这些释放的分子可能作用于内皮细胞。为了更好地解决这个问题,我们研究了富含 Co-Cr 的培养基对内皮细胞(HUVEC)的影响,考虑到一个生物学模型,使这些细胞受到剪切力的影响,以部分模拟生理环境,并进一步研究负责驱动细胞骨架重排、细胞活力和细胞外基质(ECM)重塑过程的细胞内途径。考虑到对金属蛋白酶(MMPs)活性的分析,我们的数据表明,富含 CoCr 的培养基会引起强烈的 ECM 重塑,这表明在 ECM 重塑是细胞生长的必要条件的情况下,它可能在血管生成中发挥作用。通过揭示其对 MAPK 家族成员的 mRNA 表达和蛋白水平的改变的影响,更好地解决了这个问题。此外,富含 Co-Cr 的培养基对细胞内 CDK4 基因的表达进行了调节,而 P15 和 P21 表达的调节表明需要一个重要的调节机制。总的来说,我们的结果表明,CoCr 元素的痕迹触发了受剪切力影响的内皮细胞中的决定性细胞内信号转导,这表明对与血管生成相关的机制有影响,并为 CoCr 的生物学活性提供了新的见解,因为它已作为一种有趣的生物医学材料在医学和牙科领域中脱颖而出。

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