Versican facilitates chondrocyte differentiation and regulates joint morphogenesis

• Main Authors: Choocheep K., Hatano S., Takagi H., Watanabe H., Kimata K., Kongtawelert P.
• Format: Article
• Language: English
• Published: 2014
• Online Access: http://www.scopus.com/inward/record.url?eid=2-s2.0-77954225772&partnerID=40&md5=04bbabbe991cc72081072885f69d006f; http://cmuir.cmu.ac.th/handle/6653943832/3645
• Institution: Chiang Mai University

Versican/PG-M is a large chondroitin sulfate proteoglycan in the extracellular matrix, which is transiently expressed in mesenchymal condensation areas during tissue morphogenesis. Here, we generated versican conditional knock-out mice Prx1-Cre/Vcanflox/flox, in which Vcan is pruned out by site-specific Cre recombinase driven by the Prx1 promoter. Although Prx1-Cre/Vcanflox/flox mice are viable and fertile, they develop distorted digits. Histological analysis of newborn mice reveals hypertrophic chondrocytic nodules in cartilage, tilting of the joint, and a slight delay of chondrocyte differentiation in digits. By immunostaining, whereas the joint interzone of Prx1-Cre/Vcan+/+ shows an accumulation of TGF-β, concomitant with versican, that of Prx1-Cre/Vcanflox/flox without versican expression exhibits a decreased incorporation of TGF-β. In a micromass culture system of mesenchymal cells from limb bud, whereas TGF-β and versican are co-localized in the perinodular regions of developing cartilage in Prx1-Cre/Vcan+/+, TGF-β is widely distributed in Prx1-Cre/Vcanflox/flox. These results suggest that versican facilitates chondrogenesis and joint morphogenesis, by localizing TGF-β in the extracellular matrix and regulating its signaling. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.