Axin2 regulates chondrocyte maturation and axial skeletal development.
Axis inhibition proteins 1 and 2 (Axin1 and Axin2) are scaffolding proteins that modulate at least two signaling pathways that are crucial in skeletogenesis: the Wnt/beta-catenin and TGF-beta signaling pathways. To determine whether Axin2 is important in skeletogenesis, we examined the skeletal phenotype of Axin2-null mice in a wild-type or Axin1(+/-) background. Animals with disrupted Axin2 expression displayed a runt phenotype when compared to heterozygous littermates. Whole-mount and tissue beta-galactosidase staining of Axin2(LacZ/LacZ) mice revealed that Axin2 is expressed in cartilage tissue, and histological sections from knockout animals showed shorter hypertrophic zones in the growth plate. Primary chondrocytes were isolated from Axin2-null and wild-type mice, cultured, and assayed for type X collagen gene expression. While type II collagen levels were depressed in cells from Axin2-deficient animals, type X collagen gene expression was enhanced. There was no difference in BrdU incorporation between null and heterozygous mice, suggesting that loss of Axin2 does not alter chondrocyte proliferation. Taken together, these findings reveal that disruption of Axin2 expression results in accelerated chondrocyte maturation. In the presence of a heterozygous deficiency of Axin1, Axin2 was also shown to play a critical role in craniofacial and axial skeleton development.
Dao
Debbie Y
DY
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, New York 14642, USA.
Yang
Xue
X
Flick
Lisa M
LM
Chen
Di
D
Hilton
Matthew J
MJ
O'Keefe
Regis J
RJ
D000818:Animals; D060466:Axin Protein; D001846:Bone Development / Q000235:genetics*; D001842:Bone and Bones / Q000196:embryology* / Q000473:pathology; D002356:Cartilage / Q000166:cytology* / Q000196:embryology*; D019902:Chondrocytes / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics; D024121:Collagen Type X / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006132:Growth Plate / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
D060466:Axin Protein; C111729:Axin2 protein, mouse; D024043:Collagen Type II; D024121:Collagen Type X; D003598:Cytoskeletal Proteins