Integrin-dependent signal cascades in chondrocyte mechanotransduction.

Abstract

Mechanical forces influence chondrocyte metabolism and are critically important for maintenance of normal cartilage structure and integrity. In cells of the musculoskeletal system and mechanoresponsive cells in other tissues, integrins seem to be involved in the mechanotransduction process. Integrin activity is important in the early cellular responses to mechanical stimulation, regulating activation of a number of intracellularcascades that induce changes in gene expression and tissue remodeling. In normal human articular chondrocytes, integrin activation, consequent to mechanical stimulation in vitro, results in tyrosine phosphorylation of regulatory proteins and subsequent secretion of autocrine and paracrine acting soluble mediators including substance P and interleukin 4. Significant differences in signaling events and cellular responses are seen when normal and osteoarthritic chondrocytes are mechanically stimulated. These differences may relate to differences in integrin expression and function. Improved comprehension of how integrins mediate chondrocyte responses to mechanical stimulation, and how cross talk between integrin signaling, extracellular matrix, and autocrine/paracrine signaling molecules regulate mechanotransduction and cellular reactions are necessary for further understanding of how load influences cartilage structure.