title: Smad1 plays an essential role in bone development and postnatal bone formation.
abstract: OBJECTIVE
  To determine the role of Smad1 in bone development and postnatal bone formation.
  
  
  METHODS
  Col2a1-Cre transgenic mice were bred with Smad1(fx/fx) mice to produce chondrocyte-specific Smad1 conditional knockout (cKO) mice. Embryonic skeletal preparation and staining were performed, alkaline phosphatase activity (ALP) and relative gene expression were examined in isolated primary cells. Smad1(fx/fx) mice were also bred with Col1a1-Cre transgenic mice to produce osteoblast-specific Smad1 cKO mice. Postnatal bone formation was assessed by micro-computed tomography (μCT) and histological analyses in 2-month-old mice. Mineralized bone nodule formation assay, 5-bromo-2'-deoxy-uridine (BrdU) labeling and gene expression analysis were performed.
  
  
  RESULTS
  Mice with chondrocyte- and osteoblast-specific deletion of the Smad1 gene are viable and fertile. Calvarial bone development was delayed in chondrocyte-specific Smad1 cKO mice. In osteoblast-specific Smad1 cKO mice, BMP signaling was partially inhibited and mice developed an osteopenic phenotype. Osteoblast proliferation and differentiation were impaired in osteoblast-specific Smad1 cKO mice.
  
  
  CONCLUSIONS
  Smad1 plays an essential role in bone development and postnatal bone formation.
authors.affiliation: Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Jin
authors.forename: D
authors.initials: D
authors.lastname: Tang
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.forename: M J
authors.initials: MJ
authors.lastname: Zuscik
authors.forename: D
authors.initials: D
authors.lastname: Chen
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001846:Bone Development / Q000502:physiology*; D024043:Collagen Type II / Q000235:genetics; D020869:Gene Expression Profiling; D051379:Mice; D008822:Mice, Transgenic; D051898:Smad1 Protein / Q000502:physiology*; D014129:Trabecular Meshwork / Q000648:ultrastructure; D055114:X-Ray Microtomography
chemical_list: C447413:Col2a1 protein, mouse; D024043:Collagen Type II; D051898:Smad1 Protein; D000469:Alkaline Phosphatase