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The CREB family of activators is required for endochondral bone development

Academic Article
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Overview

authors

  • Long, F. X.
  • Schipani, E.
  • Asahara, Hiroshi
  • Kronenberg, H.
  • Montminy, M.

publication date

  • February 2001

journal

  • Development  Journal

abstract

  • We have evaluated the importance of the CREB family of transcriptional activators for endochondral bone formation by expressing a potent dominant negative CREB inhibitor (A-CREB) in growth plate chondrocytes of transgenic mice. A-CREB transgenic mice exhibited short-limbed dwarfism and died minutes after birth, apparently due to respiratory failure from a diminished rib cage circumference. Consistent with the robust Ser133 phosphorylation and, hence, activation of CREB in chondrocytes within the proliferative zone of wild-type cartilage during development, chondrocytes in A-CREB mutant cartilage exhibited a profound decrease in proliferative index and a delay in hypertrophy. Correspondingly, the expression of certain signaling molecules in cartilage, most notably the Indian hedgehog (Ihh) receptor patched (Ptch), was lower in A-CREB expressing versus wild-type chondrocytes. CREB appears to promote Ptch expression in proliferating chondrocytes via an Ihh-independent pathway; phospho-CREB levels were comparable in cartilage from Ihh(-/-) and wild-type mice. These results demonstrate the presence of a distinct signaling pathway in developing bone that potentiates Ihh signaling and regulates chondrocyte proliferation, at least in part, via the CREB family of activators.

subject areas

  • Animals
  • Bone Development
  • Bone and Bones
  • Cell Division
  • Cells, Cultured
  • Chick Embryo
  • Chondrocytes
  • Collagen
  • Cyclic AMP Response Element-Binding Protein
  • Embryonic and Fetal Development
  • Gene Expression Regulation, Developmental
  • Genetic Vectors
  • Growth Plate
  • Hedgehog Proteins
  • In Situ Hybridization
  • Mice
  • Mice, Transgenic
  • Mutation
  • Phosphorylation
  • Promoter Regions, Genetic
  • Proteins
  • Signal Transduction
  • Trans-Activators
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Research

keywords

  • CREB
  • Indian hedgehog
  • bone
  • mouse
  • phosphorylation
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Identity

International Standard Serial Number (ISSN)

  • 0950-1991

PubMed ID

  • 11171337
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Additional Document Info

start page

  • 541

end page

  • 550

volume

  • 128

issue

  • 4

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