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Updated: Aug 9, 2026

Visualization of Chondrocyte Intercalation and Directional Proliferation via Zebrabow Clonal Cell Analysis in the Embryonic Meckel’s Cartilage
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Visualization of Chondrocyte Intercalation and Directional Proliferation via Zebrabow Clonal Cell Analysis in the Embryonic Meckel’s Cartilage

Published on: October 21, 2015

The CREB family of activators is required for endochondral bone development

F Long1, E Schipani, H Asahara

  • 1The Salk Institute for Biological Studies, Peptide Biology Laboratories, La Jolla, CA 92037, USA.

Development (Cambridge, England)
|February 15, 2001
PubMed

Insights

The CREB (cAMP response element-binding protein) family is crucial for endochondral bone formation. Inhibiting CREB in mice caused dwarfism and respiratory failure, highlighting its role in chondrocyte proliferation and Indian hedgehog signaling.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Skeletal Biology

Background:

  • Endochondral ossification is a complex process involving precise regulation of chondrocyte differentiation and proliferation.
  • The cAMP response element-binding protein (CREB) family of transcription factors are known regulators of cellular processes, but their specific role in skeletal development is not fully understood.

Purpose of the Study:

  • To investigate the role of the CREB family of transcriptional activators in endochondral bone formation.
  • To elucidate the molecular mechanisms by which CREB influences chondrocyte behavior during skeletal development.

Main Methods:

  • Generation of transgenic mice expressing a dominant-negative CREB inhibitor (A-CREB) specifically in growth plate chondrocytes.
  • Phenotypic analysis of A-CREB transgenic mice, including skeletal morphology and survival rates.
  • Assessment of chondrocyte proliferation, hypertrophy, and expression of key signaling molecules (e.g., Indian hedgehog receptor patched) in mutant and wild-type cartilage.

Main Results:

  • A-CREB transgenic mice displayed severe short-limbed dwarfism and perinatal lethality, likely due to respiratory failure from a compromised rib cage.
  • Chondrocytes in A-CREB mutant cartilage showed significantly reduced proliferation and delayed hypertrophy compared to wild-type controls.
  • Expression of the Indian hedgehog (Ihh) receptor patched (Ptch) was notably decreased in A-CREB expressing chondrocytes.
  • CREB appears to regulate Ptch expression in proliferating chondrocytes through an Ihh-independent pathway.

Conclusions:

  • The CREB family of activators plays a critical role in regulating chondrocyte proliferation and differentiation during endochondral bone formation.
  • A distinct signaling pathway involving CREB potentiates Indian hedgehog signaling and influences chondrocyte behavior in developing bone.
  • Targeting CREB signaling may offer therapeutic potential for skeletal development disorders.

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