Connective tissue as an integral system: role of cell-cell and cell-matrix interactions

We have applied the systems approach, to the analysis of mechanisms whereby connective tissue (CT) is integrated into one functional system. The primary CT functions in health and in disease (biomechanical, trophic, protective, reparative, and morphogenetic) are carried out by means of cell-cell, cell-matrix and intertissue interactions based on feedback between these components. Both CT as a whole and its cellular and extracellular elements exhibit structural and functional heterogeneity which increases the capacity of CT for adaptation. The intercellular interactions take place via soluble and insoluble mediators, direct cellular contacts, and cell/matrix degradation products. Results of this study support the concept of internal "network" regulation of the CT composition, functions and growth through intercellular interactions at different structural levels. Feedback mechanisms between degradation and production of collagen and interactions between collagen, macrophages and fibroblasts play a special role in the self-regulation of reparative CT growth. Collagen restores an impaired self-regulation and exerts a marked therapeutic effect on wounds, burns, trophic ulcers, and other lesions. A similar function may be performed by other matrix components and degradation/secretion products of macrophages and fibroblasts.