Effect of fluid flow-induced shear stress on human mesenchymal stem cells: differential gene expression of IL1B and MAP3K8 in MAPK signaling.

Human bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into numerous cell lineages, making them ideal for tissue engineering. Mechanical forces and mechanotransduction are important factors influencing cell responses, although such data are limited for MSCs. We investigated the effect of different profiles of fluid flow-induced shear stress on mitogen-activated protein kinase (MAPK) signaling pathway gene expression in MSCs using DNA microarray and quantitative real-time reverse transcription-PCR analysis. In response to different magnitudes and durations of fluid flow-induced shear stress, we observed significant differential gene expression for various genes in the MAPK signaling pathway. Independent of magnitude and duration, shear stress induced consistent and marked up-regulation of MAP kinase kinase kinase 8 (MAP3K8) and interleukin-1 beta (IL1B) [2-fold to >35-fold, and 4-fold to >50-fold, respectively]. We also observed consistent up-regulation of dual specificity phosphatase 5 and 6, growth arrest and DNA-damage-inducible alpha and beta, nuclear factor kappa-B subunit 1, Jun oncogene, fibroblast growth factor 1, and platelet-derived growth factor alpha. Our data support MAP3K8-induced activation of different MAPK signaling pathways in response to different profiles of shear stress, possibly as a consequence of shear-induced IL1B expression. Thus, MAP3K8 may be an important mediator of intracellular mechanotransduction in human MSCs.