TY - JOUR
T1 - Whole-genome expression analysis of human mesenchymal stromal cells exposed to ultrasmooth tantalum vs. titanium oxide surfaces
AU - Stiehler, Claudia
AU - Bünger, Cody
AU - Overall, Rupert W.
AU - Royer, Loïc
AU - Schroeder, Michael
AU - Foss, Morten
AU - Besenbacher, Flemming
AU - Kruhøffer, Mogens
AU - Kassem, Moustapha
AU - Günther, Klaus Peter
AU - Stiehler, Maik
PY - 2013/6/1
Y1 - 2013/6/1
N2 - 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®). 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.
AB - 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®). 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.
KW - Biocompatibility
KW - Cell culture
KW - Cell differentiation
KW - Cell proliferation
KW - EGR1
KW - Gene expression
KW - IRF-1
KW - IRF-8
KW - Mesenchymal stem cell
KW - NF-Y
KW - NRF2
KW - Osteoblast
KW - Oxidative stress
KW - p53
KW - Pathway analysis
KW - Tantalum
KW - Titanium
UR - http://www.scopus.com/inward/record.url?scp=84879505571&partnerID=8YFLogxK
U2 - 10.1007/s12195-012-0255-6
DO - 10.1007/s12195-012-0255-6
M3 - Journal article
AN - SCOPUS:84879505571
SN - 1865-5025
VL - 6
SP - 199
EP - 209
JO - Cellular and Molecular Bioengineering
JF - Cellular and Molecular Bioengineering
IS - 2
ER -