title: Chondrocyte-specific inhibition of β-catenin signaling leads to dysplasia of the caudal vertebrae in mice.
abstract: METHODS
  To inhibit β-catenin specifically signaling in chondrocytes Col2-ICAT transgenic mice were generated. Anomalies in caudal vertebrae were detected during embryonic and postnatal stages of Col2-ICAT transgenic mice.
  
  
  OBJECTIVE
  To determine the role of canonical β-catenin signaling in caudal vertebral development.
  
  
  BACKGROUND
  β-catenin signaling plays a critical role in skeletal development. Col2-ICAT transgenic mice were generated to selectively block β-catenin signaling by overexpression of the ICAT gene in chondrocytes.
  
  
  METHODS
  Tails of E16.5 transgenic embryos and adult Col2-ICAT transgenic mice and their wild-type littermates were collected and analyzed. Skeletal preparation, 3-dimensional micro-computed tomographic and histological analyses were performed to evaluate changes in the structure of caudal vertebrae. Bromodeoxyuridine labeling was performed to evaluate changes in chondrocyte proliferation in caudal vertebrae.
  
  
  RESULTS
  Skeletal preparation and 3-dimensional micro-computed tomographic analyses revealed bone deformation and angulated deformities in tail tissue in Col2-ICAT transgenic mice. Histological studies revealed abnormal bone development and dysplastic caudal vertebrae in Col2-ICAT transgenic mice. Inhibition of β-catenin signaling in cartilage resulted in vertebral dysplasia leading to aberrant resegmenting process. Thus, 2 poorly developed sclerotomes failed to fuse to form a complete vertebrae. BrdU labeling revealed a decreased chondrocyte proliferation in both cartilageous templates of transgenic embryos and the growth plate of adult Col2-ICAT transgenic mice.
  
  
  CONCLUSIONS
  Wnt/β-catenin signaling plays an important role in vertebral development. Inhibition of β-catenin signaling in chondrocytes results in caudal vertebra deformity in mice, which may occur as early as in the stage of sclerotome formation.
  
  
  METHODS
  N/A.
authors.affiliation: *Spine Research Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China †Department of Biochemistry, Rush University Medical Center, Chicago, IL; and ‡Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Bing
authors.initials: B
authors.lastname: Shu
authors.forename: Tian-Fang
authors.initials: TF
authors.lastname: Li
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.forename: De-Zhi
authors.initials: DZ
authors.lastname: Tang
authors.forename: Yejia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D024043:Collagen Type II / Q000235:genetics; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins; D015398:Signal Transduction; D013131:Spine / Q000002:abnormalities / Q000000981:diagnostic imaging / Q000378:metabolism*; D013623:Tail / Q000002:abnormalities / Q000000981:diagnostic imaging / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C447413:Col2a1 protein, mouse; D024043:Collagen Type II; C498785:Ctnnbip1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D051176:beta Catenin
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