Promotion of chondrocyte proliferation by versican mediated by G1 domain and EGF-like motifs

We have previously demonstrated that versican stimulated NIH3T3 fibroblast proliferation. Since versican is expressed in cartilage, we investigated wh ether versican plays a role in chondrocyte proliferation. We developed a te chnique to stably express a recombinant versican mini-gene in chicken chond rocytes, and its effect on chondrocyte proliferation was analyzed by the in crease in cell number. The effect of cell adhesion on cell proliferation wa s tested. Finally, the versican mini-gene was truncated to assess the role of ECF-like motifs in cell proliferation. Expression of the recombinant ver sican mini-gene stimulated chondrocyte proliferation. Antisense oligonucleo tides complementary to versican inhibited chondrocyte proliferation. The G1 domain of versican stimulated chondrocyte proliferation by destabilizing c hondrocyte adhesion. Furthermore, deletion of the two EGF-like motifs from the G3 domain also reduced the function of versican in stimulating cell pro liferation. Versican enhances chondrocyte proliferation through a mechanism involving its G1 and G3 domains. This finding may have implications for ou r understanding of the pathogenesis of various joint diseases. (C) 1999 Wil ey-Liss, Inc.