AGGRECAN AND LINK PROTEIN AFFECT CELL-ADHESION TO CULTURE PLATES AND TO TYPE-II COLLAGEN

Cartilage is a hypocellular tissue in which a balance of matrix molecu les, especially aggrecan and link protein, play a critical role in mai ntaining structural integrity. To study the role of aggrecan and link protein in mediating cell activities, we have stably expressed them in NIH/3T3 fibroblasts and observed the effect on cell-substratum intera ctions. Overexpression of either protein destabilized the cell-substra tum interaction. However, when both were co-expressed, the interaction between cell and substratum was less impaired. Similar results were o btained on type II collagen-coated plates. The addition of exogenous g ene products into fibroblast cell lines and chondrocyte culture had th e same effect as expression of the genes. The addition of exogenous hy aluronan to the growth medium or treatment of cells with hyaluronidase also decreased cell adhesion, indicating that hyaluronan also plays a role in the cell-substratum adhesion. The presence of aggrecan seems to increase the amount of link protein on the cell surface. Chondrocyt es expressing high concentrations of aggrecan and link protein were ma intained within a matrix network and were able to survive in suspended culture. Imbalances in aggrecan or link protein concentrations, or de gradation of hyaluronan, disrupted the network and caused the chondroc ytes to aggregate or adhere to the plates.