Versican facilitates chondrocyte differentiation and regulates joint morphogenesis.
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/Vcan(flox/flox), in which Vcan is pruned out by site-specific Cre recombinase driven by the Prx1 promoter. Although Prx1-Cre/Vcan(flox/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-beta, concomitant with versican, that of Prx1-Cre/Vcan(flox/flox) without versican expression exhibits a decreased incorporation of TGF-beta. In a micromass culture system of mesenchymal cells from limb bud, whereas TGF-beta and versican are co-localized in the perinodular regions of developing cartilage in Prx1-Cre/Vcan(+/+), TGF-beta is widely distributed in Prx1-Cre/Vcan(flox/flox). These results suggest that versican facilitates chondrogenesis and joint morphogenesis, by localizing TGF-beta in the extracellular matrix and regulating its signaling.
Choocheep
Kanyamas
K
Institute for Molecular Science of Medicine, Aichi Medical University, Karimata 21, Yazako, Nagakute, Aichi 480-1195, Japan.
Hatano
Sonoko
S
Takagi
Hidekazu
H
Watanabe
Hiroki
H
Kimata
Koji
K
Kongtawelert
Prachya
P
Watanabe
Hideto
H
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured / Q000166:cytology / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology*; D002810:Chondroitinases and Chondroitin Lyases / Q000378:metabolism; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D006820:Hyaluronic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D007596:Joints / Q000254:growth & development*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D017384:Sequence Deletion; D016212:Transforming Growth Factor beta / Q000502:physiology; D053675:Versicans / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D018398:Homeodomain Proteins; C489936:Prrx1 protein, mouse; D016212:Transforming Growth Factor beta; D053675:Versicans; D006820:Hyaluronic Acid; D004247:DNA; D002810:Chondroitinases and Chondroitin Lyases
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