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Abstract
Extracellular matrix (ECM) is the substrate for cell adhesion, growth, and differentiation,
and it provides mechanical support to tissues. It is well known that connective tissue
cells adapt their ECM to changes in mechanical load, as seen, e.g. during bone remodeling
or wound healing. A feedback mechanism must exist by which cells that sense mechanical
stress via their substrate respond by an altered pattern of protein expression, and
thus remodel the ECM to meet changing mechanical requirements. What signals are triggered
in connective tissue cells by mechanical stress, and how do such stimuli affect the
expression of specific ECM proteins? The evidence will be reviewed that integrins,
the transmembrane adhesion and signaling receptors which physically link ECM to the
cytoskeleton, might be key players in transducing mechanical signals, presumably via
MAP kinase and NF-kappaB pathways. At the far end of the response, there is evidence
for regulation at the level of gene transcription. For example, the production of
tenascin-C and collagen XII, two ECM proteins typical of tendons and ligaments, is
high in fibroblasts attached to a stretched collagen matrix, but suppressed in cells
on a relaxed matrix. The response to a change in stretch is rapid and reversible,
and is reflected on the mRNA level. Both the tenascin-C and the collagen XII gene
promoters contain 'stretch-responsive' enhancer regions with similarity to 'shear
stress response elements' in other genes. The precise signal pathways converging on
these mechano-responsive enhancer elements remain to be elucidated.