Elsevier

Experimental Cell Research

Volume 263, Issue 1, 1 February 2001, Pages 33-42
Experimental Cell Research

Regular Article
Versican Modulates Embryonic Chondrocyte Morphology via the Epidermal Growth Factor-like Motifs in G3

https://doi.org/10.1006/excr.2000.5095Get rights and content

Abstract

This investigation was designed to characterize the effect of the extracellular matrix molecule versican on chondrocyte morphology, using the well-studied chondrocyte cell culture system. When cultured chondrocytes reverted or “dedifferentiated” to a fibroblast-like morphology, we found that versican expression was significantly enhanced. Transfection of chondrocytes, isolated from embryonic chicken sterna, with a chicken miniversican construct accelerated the reversionprocess, while expression of an antisense construct inhibited it. A mutant miniversican lacking two epidermal growth factor-like motifs (versicanΔEGF) promoted differentiation, as shown by morphological changes and changes in the expression of other extracellular matrix molecules. A truncated versican mutant, the G3ΔEGF, a G3 domain lacking its two epidermal growth factor-like motifs, also enhanced differentiation. This effect is related to G3ΔEGF-induced change in cytoskeleton, since transfected cells exhibited misassembly of actin filaments. This article thus provides the first evidence that versican modulates chondrocyte morphology via changes in cytoskeletal structure, and may imply that extracellular matrix molecules play an important role in cell differentiation.

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      Versican is the principal chondroitin sulfate proteoglycan in blood vessels, as well as in the intima and adventitia of most arteries and veins [10]. In vitro studies have shown that versican modulates cell adhesion [11], aggregation [12], migration [13], proliferation [14], morphogenesis [15,16], and tissue angiogenesis [17]. This study was designed to explore the roles of versican in the process of dermal wound repair.

    • Proteoglycan degradation by the ADAMTS family of proteinases

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      There is continuing intrigue and speculation amongst the research community that this fragment, and other catalytic fragments of proteoglycan substrates, might have unique biological properties that are not invested in the parent molecules. Indeed, recombinant single domains of versican appear to have bioactivity in cell culture systems [182–184]. Proteoglycans in extracellular matrices are degraded by ADAMTS enzymes in many and varied biological situations.

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