Versican Facilitates Chondrocyte Differentiation and Regulates Joint Morphogenesis |
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Authors: | Kanyamas Choocheep Sonoko Hatano Hidekazu Takagi Hiroki Watanabe Koji Kimata Prachya Kongtawelert Hideto Watanabe |
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Institution: | From the ‡Institute for Molecular Science of Medicine, Aichi Medical University, Karimata 21, Yazako, Nagakute, Aichi 480-1195, Japan and ;the §Thailand Excellence Center for Tissue Engineering, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand |
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Abstract: | 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. |
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Keywords: | Development Glycosaminoglycan Proteoglycan Structure Proteoglycan Synthesis Transforming Growth Factor Beta (TGFbeta) Cartilage Development Chondrocyte Differentiation Joint Morphogenesis Versican |
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