Regulation of extracellular matrix synthesis by mechanical stress.

The extracellular matrix (ECM) provides mechanical support to tissues and is a substrate for cell adhesion and differentiation. Cells bind to ECM via specific cell surface receptors such as integrins. When engaging with ECM ligands, these receptors can activate signal transduction pathways within the cells and may act as mechanochemical transducers. Thus, interaction of cells with ECM can modulate gene expression although the exact mechanisms are not known. Among the genes that are, in part, controlled by cell-ECM interactions are those for certain ECM components themselves. Bone cells, for example, remodel their matrix and reorient bone trabeculae in response to mechanical strain. Recently, we found that fibroblasts attached to a strained collagen matrix produce more of the ECM glycoproteins tenascin and collagen XII than cells in a relaxed matrix. In vivo, these two proteins are specifically expressed in places where mechanical strain is high. We also showed that the chick tenascin gene promoter contains a novel cis-acting, "strain-responsive" element that causes enhanced transcription in cells attached to a strained collagen matrix. Similar enhancer elements might be present in the promoters of other genes induced by mechanical stress. It can be speculated that connective tissue cells sense force vectors in their ECM environment and react to altered mechanical needs by regulating the transcription of specific ECM genes; this process is a prerequisite for matrix remodeling.