The roles of matrix molecules in mediating chondrocyte aggregation, attachment, and spreading

The most abundant macromolecules in cartilage are hyaluronan, collagen, aggrecan, and link protein, which are believed to play roles in maintaining a unique three-dimensional network for a functional joint. This study was designed to investigate the roles of the major extracellular molecules in mediating chondrocyte-matrix interactions. We employed specific approaches to remove components individually or in combination: hyaluronan was digested with hyaluronidase; type II collagen was digested with collagenase; aggrecan expression was inhibited with antisense and beta-xyloside approaches; and link protein expression was inhibited with antisense oligonucleotides. Digestion of hyaluronan induced chondrocyte attachment to tissue culture plates, collagen-coated plates, and fibroblast-like chondrocyte cultures, and induced chondrocyte aggregation. Treated chondrocytes exhibited a fibroblast-like morphology, and the effects of hyaluronidase were dose-dependent. Conversely, the effect of collagenase on chondrocyte adhesion and aggregation was far less pronounced. Treatment with Arg-Gly-Asp peptide inhibited chondrocyte-collagen interaction. Chondrocyte attachment was enhanced by antisense oligonucleotides complementary to aggrecan and link protein and by beta-xyloside treatment. Nevertheless, hyaluronan seems to predominate over the other molecules in mediating chondrocyte-matrix interactions.