Interactions of connective tissue cells with the extracellular matrix.

Interactions between cells and extracellular matrix components have been shown to be crucial for the regulation of tissue differentiation and function in a range of organisms. Recent work has defined several families of receptors by their domain structure, and the peptide sequence motifs in the ligands which they recognize have been elucidated. Thus, the integrin fibronectin receptor has been shown to recognize "RGD" and other sequences within matrix and plasma proteins. Disruption of these integrin-ligand interactions by gene inactivation via homologous recombination of receptor or ligand, and by use of RGD inhibitors or antibodies, modifies embryonic development and cellular function. Recent evidence from several receptor systems has also demonstrated that they can partake in signal transduction, in addition to adhesive events, leading to the definition of further functional activities. The range of receptors and their ligands involved in matrix interactions and data on their role in a variety of cellular systems are summarized. The therapeutic implications of a fundamental approach to cellular adhesion processes will be highlighted by considering the role of the alpha v beta 3 integrin receptor in osteoclastic bone resorption.