title: Intervertebral disc development is regulated by Wnt/β-catenin signaling.
abstract: METHODS
  Histologic analysis of intervertebral disc (IVD) in three types of transgenic mice.
  
  
  OBJECTIVE
  To investigate the role of Wnt/β-catenin signaling in regulation of IVD development and organization.
  
  
  BACKGROUND
  β-catenin dependent Wnt signaling is one of the central regulators in cartilage development during limb skeletal formation. Little is known, however, about the physiologic relevance of this signaling pathway to IVD development and organization.
  
  
  METHODS
  Temporal-spatial distribution of Wnt/β-catenin signaling activity was examined in IVD using Wnt/β-catenin reporter (TOPGAL) mice. The structural changes in the mouse IVD components such as the nucleus pulposus (NP), endplate (EP), annulus fibrosus (AF), and the growth plate (GP) of the vertebral body were analyzed after transient activation of Wnt/β-catenin signaling or deletion of β-catenin in the mice.
  
  
  RESULTS
  Activity of Wnt/β-catenin signaling was high in EP, AF, and GP in the embryonic stages and decreased at the postnatal stage; it was undetectable in the embryonic NP but upregulated after birth. The transient activation of Wnt/β-catenin signaling caused severe deterioration of the GP and the AF, whereas deficiency of β-catenin accelerated bone formation in between EP and GP.
  
  
  CONCLUSIONS
  The findings in this study suggest that proper regulation of Wnt/β-catenin signaling is required for development and organization of IVD.
authors.affiliation: Department of Orthopaedic Surgery, Thomas Jefferson University, College of Medicine, Philadelphia, PA, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kondo
authors.forename: Takahito
authors.initials: T
authors.lastname: Yuasa
authors.forename: Kengo
authors.initials: K
authors.lastname: Shimono
authors.forename: Weien
authors.initials: W
authors.lastname: Tung
authors.forename: Takahiro
authors.initials: T
authors.lastname: Okabe
authors.forename: Rika
authors.initials: R
authors.lastname: Yasuhara
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pacifici
authors.forename: Yejia
authors.initials: Y
authors.lastname: Zhang
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwamoto
authors.forename: Motomi
authors.initials: M
authors.lastname: Enomoto-Iwamoto
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D005260:Female; D006651:Histocytochemistry; D017403:In Situ Hybridization; D007403:Intervertebral Disc / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D050071:Bone Density Conservation Agents; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D051176:beta Catenin; D013629:Tamoxifen