EXPRESSION OF THE G1 DOMAIN OF AGGRECAN INTERFERES WITH CHONDROCYTE ATTACHMENT AND ADHESION

The proteoglycan aggrecan is a major component of cartilage, and degra dation of aggrecan is associated with aging and a number of pathologic al conditions. To investigate the effects of the accumulation of G1 do main from degraded aggrecan, we overexpressed the G1 domain in cell cu lture. Exogenous addition of the expressed GI gene product to chondroc yte cultures retarded the attachment of chondrocytes to tissue culture plates, type II collagen and hyaluronan. Expression of the G1 constru ct, aggrecan or link protein in chondrocytes led to decreased cell adh esion. Interestingly, aggrecan land specifically G1) and link protein, when applied simultaneously, seem to be able to interact and inhibit the destabilization of chondrocyte adhesion observed when either is ap plied alone. The G3 domain of aggrecan has little effect on chondrocyt e adhesion and did not change the effects of link protein and the G1 d omain on chondrocyte adhesion. These effects probably involve the bind ing of G1 to cell surface molecules, since FAGS (fluorescence-activate d cell sorter) analysis demonstrated that the G1 domain binds to the c hondrocyte surface with high affinity.