Differential Gene Expression of Integrins Alpha 2 and Beta 8 in Human Mesenchymal Stem Cells Exposed to Fluid Flow

Abstract

Human bone marrow-derived mesenchymal stem cells (MSCs) have potential applications for tissue engineering because they can differentiate into numerous cell lineages. Mechanical forces and mechanotransduction are important factors influencing cell responses, although such data are limited for MSCs. We investigated the gene expression response of integrin and extracellular matrix (ECM) genes in MSCs exposed to different magnitudes (1, 5, and 10 dyn/cm2) and durations (10 min, 1 h, and 24 h) of fluid flow-induced shear stress. Gene expression was examined using microarray and quantitative real-time RT-PCR analysis. In response to different magnitudes and durations of shear stress, we observed significant differential gene expression for two integrin genes: consistent up-regulation of integrin α2 subunit (ITGA2) [2- to 18-fold] and consistent down-regulation of integrin β8 subunit (ITGB8) [2- to 9-fold]. There was also evidence of ECM gene down-regulation, namely collagen type XI α1 (COL11A1), COL14A1, and COL21A1 (2- to 4-fold for each), and laminin α4 (LAMA4) [2- to 5-fold]. This indicates specific modulation of integrin gene expression in response to shear stress, supporting altered cell–ECM interactions and integrin-mediated mechanotransduction. These findings further our understanding of how mechanical stimuli regulate MSC behavior, which will be important in the development of mechanical conditioning strategies for tissue engineering.