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 whether versican plays a role in chondrocyte proliferation. We developed a technique to stably express a recombinant versican mini-gene in chicken chondrocytes, and its effect on chondrocyte proliferation was analyzed by the increase in cell number. The effect of cell adhesion on cell proliferation was tested. Finally, the versican mini-gene was truncated to assess the role of EGF-like motifs in cell proliferation. Expression of the recombinant versican mini-gene stimulated chondrocyte proliferation. Antisense oligonucleotides complementary to versican inhibited chondrocyte proliferation. The G1 domain of versican stimulated chondrocyte proliferation by destabilizing chondrocyte adhesion. Furthermore, deletion of the two EGF-like motifs from the G3 domain also reduced the function of versican in stimulating cell proliferation. Versican enhances chondrocyte proliferation through a mechanism involving its G1 and G3 domains. This finding may have implications for our understanding of the pathogenesis of various joint diseases.
Zhang
Y
Y
Sunnybrook & Women's College Health Sciences Centre and Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada.
Cao
L
L
Kiani
C
C
Yang
B L
BL
Hu
W
W
Yang
B B
BB
D020816:Amino Acid Motifs / Q000235:genetics / Q000502:physiology; D000818:Animals; D002450:Cell Communication / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000502:physiology*; D037181:Lectins, C-Type; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D053675:Versicans
D011508:Chondroitin Sulfate Proteoglycans; D037181:Lectins, C-Type; D010446:Peptide Fragments; D011994:Recombinant Proteins; D053675:Versicans; D004815:Epidermal Growth Factor