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Indian Hedgehog produced by postnatal chondrocytes is essential for maintaining a growth plate and trabecular bone

Yukiko Maeda1, Eiichiro Nakamura, Minh-Thanh Nguyen

  • 1Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.

Proceedings of the National Academy of Sciences of the United States of America
|April 6, 2007
PubMed

Insights

Indian hedgehog (Ihh) is crucial for bone development. Postnatal deletion of Ihh in mice caused growth plate abnormalities, dwarfism, and bone loss, highlighting its role in maintaining skeletal growth and articular surfaces.

Area of Science:

  • Skeletal Biology
  • Developmental Biology
  • Genetics

Background:

  • Indian hedgehog (Ihh) is vital for prenatal bone formation.
  • Previous studies were limited by early lethality in Ihh-ablated mice.
  • The role of Ihh in postnatal bone development remained unclear.

Purpose of the Study:

  • To investigate the function of Indian hedgehog (Ihh) in postnatal skeletal development.
  • To characterize a novel mouse model with temporal and spatial deletion of Ihh in chondrocytes.

Main Methods:

  • Generation of a mouse model with conditional postnatal deletion of the Ihh gene in chondrocytes.
  • Analysis of growth plate morphology, articular surface integrity, and bone structure.
  • Assessment of Wnt signaling in osteoblastic cells.

Main Results:

  • Postnatal Ihh deletion led to growth plate disorganization, premature vascular invasion, and ectopic chondrocytes.
  • Mutant mice displayed articular surface destruction, growth plate fusion, and dwarfism.
  • Progressive trabecular bone loss was observed, correlated with reduced Wnt signaling.

Conclusions:

  • Postnatal chondrocyte-derived Ihh is essential for maintaining growth plate structure and articular surfaces.
  • Ihh signaling is required for sustained trabecular bone mass and overall skeletal growth.
  • This study elucidates the critical postnatal role of Ihh in skeletal homeostasis.

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