Versican modulates embryonic chondrocyte morphology via the epidermal growth factor-like motifs in G3

This investigation was designed to characterize the effect of the extracell ular matrix molecule versican on chondrocyte morphology, using the well-stu died chondrocyte cell culture system. When cultured chondrocytes reverted o r "dedifferentiated" to a fibroblastlike morphology, we found that versican expression was significantly enhanced. Transfection of chondrocytes, isola ted from embryonic chicken sterna, with a chicken miniversican construct ac celerated the reversion process, while expression of an antisense construct inhibited it. A mutant miniversican lacking two epidermal growth factor-li ke motifs (versican Delta EGF) promoted differentiation, as shown by morpho logical changes and changes in the expression of other extracellular matrix molecules. A truncated versican mutant, the G3 Delta EGF, a G3 domain lack ing its two epidermal growth factor-like motifs, also enhanced differentiat ion. This effect is related to G3 Delta EGF-induced change in cytoskeleton, since transfected cells exhibited misassembly of actin filaments. This art icle thus provides the first evidence that versican modulates chondrocyte m orphology via changes in cytoskeletal structure, and may imply that extrace llular matrix molecules play an important role in cell differentiation. (C) 2001 Academic Press.