Whole-Genome Expression Analysis of Human Mesenchymal Stromal Cells Exposed to Ultrasmooth Tantalum vs. Titanium Oxide Surfaces: Cellular and Molecular Bioengineering

C. Stiehler, C. Bunger, R. W. Overall, L. Royer, M. Schroeder, M. Foss, F. Besenbacher, M. Kruhoffer, M. Kassem, K. P. Gunther, M. Stiehler

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Durable osseointegration of metallic bone implants requires that progenitor cells attach, proliferate and differentiate on the implant surface. Previously, we demonstrated superior biocompatibility of human mesenchymal stromal cells (MSCs) cultivated on ultrasmooth tantalum (Ta) as compared to titanium (Ti) surface. The aim of this study was to extend the previous investigation of biocompatibility by monitoring temporal gene expression of MSCs on topographically comparable smooth Ta and Ti surfaces using whole-genome gene expression analysis. Total RNA samples from telomerase-immortalized human MSCs cultivated on plain sputter-coated surfaces of Ta or Ti for 1, 2, 4, and 8 days were hybridized to n = 16 U133 Plus 2.0 arrays (Affymetrix(A (R))). Functional annotation, cluster and pathway analyses were performed. The vast majority of genes were differentially regulated after 4 days of cultivation and genes upregulated by MSCs exposed to Ta and Ti were predominantly related to the processes of differentiation and transcription, respectively. Functional annotation analysis of the 1,000 temporally most significantly regulated genes suggests earlier cellular differentiation on Ta compared to Ti surface. Key genes related to osteogenesis and cell adhesion were upregulated by MSCs exposed to Ta. We further identified differentially regulated candidate transcription factors, e.g., NRF2, EGR1, IRF-1, IRF-8, NF-Y, and p53 as well as relevant signaling pathways, e.g., p53 and mTOR, indicating e.g., differences in the Ta- and Ti-induced oxidative stress reactions at the cell/biomaterial interface. These findings suggest that Ta is a promising material for bone implants.
Original languageEnglish
JournalCellular and Molecular Bioengineering
Volume6
Pages (from-to)199-209
ISSN1865-5025
DOIs
Publication statusPublished - 2013

Keywords

  • Cell culture Gene expression Mesenchymal stem cell Osteoblast Tantalum Titanium Biocompatibility Cell differentiation Pathway analysis Cell proliferation Oxidative stress NRF2 EGR1 IRF-1 IRF-8 NF-Y p53 POROUS TANTALUM OXIDATIVE STRESS RHO-GTPASES STEM-CELLS BONE PROTEIN ROUGHNESS IMPLANTS BINDING DIFFERENTIATION

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