The g3 domain of versican inhibits mesenchymal chondrogenesis via the epidermal growth factor like motifs

Versican is a highly expressed proteoglycan in zones of developing tissues. To investigate whether versican plays a role in cell differentiation, we s tudied its role in mesenchymal condensation and chondrogenesis. Here we rep ort that a mini-versican gene product inhibits mesenchymal chondrogenesis b ut not condensation. The mini-versican-treated mesenchymal cultures form fe wer, smaller cartilaginous nodules and produced lower levels of link protei n and type II collagen. The versican G3 domain alone, but not G1, was suffi cient to inhibit mesenchymal chondrogenesis. Deletion of two epidermal grow th factor (EGF)-like motifs in the G3 domain abolished the effect of versic an, The G3 domain of aggrecan, which does not contain an EGF-like motif, di d not inhibit mesenchymal chondrogenesis, We also generated a chimera const ruct containing the two EGF-like motifs of versican and the G3 domain of ag grecan, and we observed that this chimera construct inhibited chondrogenesi s to a lesser extent than did the full-length versican G3 construct. Direct transfection of mesenchymal cells with different constructs produced simil ar results. Furthermore, treatment with versican antisense oligonucleotides and transfection with a versican antisense construct promoted chondrogenes is, Taken together, our results strongly suggest that versican inhibits mes enchymal chondrogenesis via its EGF-like motifs.