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Tissue Preparation and Immunostaining of Mouse Craniofacial Tissues and Undecalcified Bone
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Constitutive activation of smoothened leads to impaired developments of postnatal bone in mice

Eui-Sic Cho1, Shin-Saeng Lim, Jae-Won Hwang

  • 1Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences and Brain Korea 21 Program, Chonbuk National University, Jeonju 561-756, Korea.

Molecules and Cells
|September 18, 2012
PubMed

Insights

Sonic hedgehog (Shh) signaling, when overactivated via Smoothened (Smo), hinders bone development. Sustained Smo activation in mice impairs bone mineral density and suppresses key bone formation genes.

Area of Science:

  • Skeletal Biology
  • Developmental Biology
  • Molecular Signaling

Background:

  • Sonic hedgehog (Shh) signaling is crucial for organ development, including bone formation.
  • Smoothened (Smo) is a key mediator of Shh signaling, but its role in postnatal bone development requires further elucidation.

Purpose of the Study:

  • To investigate the impact of sustained Smoothened (Smo) activation on postnatal bone development.
  • To explore the molecular mechanisms by which Shh signaling affects bone formation.

Main Methods:

  • Utilized a conditional knock-in mouse model (SmoM2; OCN-Cre) expressing a constitutively active Smo.
  • Analyzed bone mineral density, growth, and gene expression of bone formation markers (Runx2, osterix, collagen I, osteocalcin) in mutant and control mice.
  • Assessed mineralization and proliferation in primary calvarial osteoblast cultures.

Main Results:

  • SmoM2; OCN-Cre mutant mice exhibited growth retardation and reduced bone mineral density.
  • Constitutive Smo activation led to decreased expression of key bone formation-related genes.
  • Suppressed mineralization was observed in calvarial osteoblasts with sustained Smo activation, without affecting proliferation.

Conclusions:

  • Sustained Smo activation inhibits postnatal bone development in mice.
  • This inhibition is mediated by the suppression of gene expression critical for bone formation.
  • Shh signaling, through Smo, plays a regulatory role in maintaining bone homeostasis postnatally.

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