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 t o ECM via specific cell surface receptors such as integrins. When enga ging with ECM ligands, these receptors can activate signal tranduction pathways within the cells and may act as mechanochemical transducers. Thus, interaction of cells with ECM can modulate gene expression alth ough the exact mechanisms are not known. Among the genes that are, in part, controlled by cell-ECM interactions are those for certain ECM co mponents 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 produ ce more of the ECM glycoproteins tenascin and collagen XII than cells in a relaxed matrix. In vivo, these two proteins are specifically expr essed in places where mechanical strain is high. We also showed that t he chick tenascin gene promoter contains a novel cis-acting, ''strain- responsive'' element that causes enhanced transcription in cells attac hed 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 regu lating the transcription of specific ECM genes; this process is a prer equisite for matrix remodeling.