Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials

TY - JOUR

T1 - Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials

AU - Autefage, Helene

AU - Gentleman, Eileen

AU - Littmann, Elena

AU - Hedegaard, Martin A. B.

AU - Von Erlach, Thomas

AU - O'Donnell, Matthew

AU - Burden, Frank R.

AU - Winkler, David A.

AU - Stevens, Molly M.

PY - 2015/4/7

Y1 - 2015/4/7

N2 - Despite the increasing sophistication of biomaterials design and functional characterization studies, little is known regarding cells' global response to biomaterials. Here, we combined nontargeted holistic biological and physical science techniques to evaluate how simple strontium ion incorporation within the well-described biomaterial 45S5 bioactive glass (BG) influences the global response of human mesenchymal stem cells. Our objective analyses of whole gene-expression profiles, confirmed by standard molecular biology techniques, revealed that strontium-substituted BG up-regulated the isoprenoid pathway, suggesting an influence on both sterol metabolite synthesis and protein prenylation processes. This up-regulation was accompanied by increases in cellular and membrane cholesterol and lipid raft contents as determined by Raman spectroscopy mapping and total internal reflection fluorescence microscopy analyses and by an increase in cellular content of phosphorylated myosin II light chain. Our unexpected findings of this strong metabolic pathway regulation as a response to biomaterial composition highlight the benefits of discovery-driven nonreductionist approaches to gain a deeper understanding of global cell-material interactions and suggest alternative research routes for evaluating biomaterials to improve their design.

AB - Despite the increasing sophistication of biomaterials design and functional characterization studies, little is known regarding cells' global response to biomaterials. Here, we combined nontargeted holistic biological and physical science techniques to evaluate how simple strontium ion incorporation within the well-described biomaterial 45S5 bioactive glass (BG) influences the global response of human mesenchymal stem cells. Our objective analyses of whole gene-expression profiles, confirmed by standard molecular biology techniques, revealed that strontium-substituted BG up-regulated the isoprenoid pathway, suggesting an influence on both sterol metabolite synthesis and protein prenylation processes. This up-regulation was accompanied by increases in cellular and membrane cholesterol and lipid raft contents as determined by Raman spectroscopy mapping and total internal reflection fluorescence microscopy analyses and by an increase in cellular content of phosphorylated myosin II light chain. Our unexpected findings of this strong metabolic pathway regulation as a response to biomaterial composition highlight the benefits of discovery-driven nonreductionist approaches to gain a deeper understanding of global cell-material interactions and suggest alternative research routes for evaluating biomaterials to improve their design.

KW - strontium-releasing biomaterials

KW - human mesenchymal stem cells

KW - microarray analysis

KW - sparse feature selection analysis

KW - mevalonate pathway

KW - MESENCHYMAL STROMAL CELLS

KW - OSTEOGENIC DIFFERENTIATION

KW - OSTEOBLAST DIFFERENTIATION

KW - MOLECULAR-MECHANISMS

KW - DESCRIPTOR SELECTION

KW - SQUALENE SYNTHASE

KW - LIPID RAFTS

KW - RANELATE

KW - OSTEOPOROSIS

KW - CHOLESTEROL

U2 - 10.1073/pnas.1419799112

DO - 10.1073/pnas.1419799112

M3 - Article

SN - 0027-8424

VL - 112

SP - 4280

EP - 4285

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 14

ER -