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

The most abundant macromolecules in cartilage are hyaluronan, collagen, agg recan, and link protein, which are believed to play roles in maintaining a unique three-dimensional network for a functional joint. This study was des igned to investigate the roles of the major extracellular molecules in medi ating chondrocyte-matrix interactions. We employed specific approaches to r emove components individually or in combination: hyaluronan was digested wi th hyaluronidase; type II collagen was digested with collagenase; aggrecan expression was inhibited with antisense and beta-xyloside approaches; and l ink protein expression was inhibited with antisense oligonucleotides. Diges tion of hyaluronan induced chondrocyte attachment to tissue culture plates, collagen-coated plates, and fibroblast-like chondrocyte cultures, and indu ced chondrocyte aggregation. Treated chondrocytes exhibited a fibroblast-li ke morphology, and the effects of hyaluronidase were dose-dependent Convers ely, the effect of collagenase on chondrocyte adhesion and aggregation was far less pronounced. Treatment with Arg-Gly-Asp peptide inhibited chondrocy te-collagen interaction. Chondrocyte attachment was enhanced by antisense o ligonucleotides complementary to aggrecan and link protein and by beta-xylo side treatment. Nevertheless, hyaluronan seems to predominate over the othe r molecules in mediating chondrocyte-matrix interactions, (C) 2000 Wiley-Li ss, Inc.