Characterizing the role of mechanical signals in gene regulatory networks using Long SAGE.

A systems understanding of mechanical regulation is critical for determining how cells proliferate and differentiate. To better understand the biological process in which mechanical signals regulate cells, we globally investigated the gene expression profiling via long serial analysis of gene expression (Long SAGE) in osteoblasts after exposure to mechanical stretching. The analysis showed that the differentially expressed genes were related with many physiological processes, including signal transduction, cell proliferation and apoptosis. Several genes that were seldom or never studied in osteoblasts have been found in this study. We further analyzed the signal pathways and provided gene regulatory networks activated by mechanical signals. Many changed genes in our data were contributed to ECM-integrin-FAK mediated pathway and mainly influenced actin-cytoskeleton dynamic remodeling, cell proliferation and differentiation. We also provided evidence supporting the hypothesis that endoplasmic reticulum and mitochondrion were combined to dedicate to calcium regulation. Taken together, our experiments provided a systemic view on biological processes and mechanotransduction network in osteoblasts, suggesting that mechanical signals regulate osteoblast through a greater diversity of interactions and pathways than previously appreciated.