Intercellular signaling pathways active during and after growth and differentiation of the lumbar vertebral growth plate

Spine (Phila Pa 1976). 2011 Jun 15;36(14):1071-80. doi: 10.1097/BRS.0b013e3181f7a3ca.

Abstract

Study design: Vertebral growth plates at different postnatal ages were assessed for active intercellular signaling pathways.

Objective: To generate a spatial and temporal map of the major signaling pathways active in the postnatal mouse lumbar vertebral growth plate.

Summary of background data: The growth of all long bones is known to occur by cartilaginous growth plates. The growth plate is composed of layers of chondrocyets that actively proliferate, differentiate, die and, are replaced by bone. The role of major cell signaling pathways has been suggested for regulation of the fetal long bones. But not much is known about the molecular or cellular signals that control the postnatal vertebral growth plate and hence postnatal vertebral bone growth. Understanding such molecular mechanisms will help design therapeutic treatments for vertebral growth disorders such as scoliosis.

Methods: Antibodies against activated downstream intermediates were used to identify cells in the growth plate responding to BMP, TGFβ, and FGF in cryosections of lumbar vertebrae from different postnatal age mice to identify the zones that were responding to these signals. Reporter mice were used to identify the chondrocytes responding to hedgehog (Ihh), and Wnt signaling.

Results: We present a spatial/temporal map of these signaling pathways during growth, and differentiation of the mouse lumbar vertebral growth plate.

Conclusion: During growth and differentiation of the vertebral growth plate, its different components respond at different times to different intercellular signaling ligands. Response to most of these signals is dramatically downregulated at the end of vertebral growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Cell Differentiation*
  • Cell Proliferation
  • Chondrocytes / metabolism
  • Extracellular Space / metabolism
  • Growth Plate / cytology
  • Growth Plate / growth & development
  • Growth Plate / metabolism*
  • Hedgehog Proteins / metabolism
  • Histones / metabolism
  • Immunohistochemistry
  • Lumbar Vertebrae / cytology
  • Lumbar Vertebrae / growth & development
  • Lumbar Vertebrae / metabolism*
  • Male
  • Mice
  • Microscopy, Confocal
  • Phosphoproteins / metabolism
  • Signal Transduction*
  • Smad Proteins / metabolism
  • Smad4 Protein
  • Time Factors
  • Wnt Proteins / metabolism
  • Xenopus Proteins

Substances

  • Hedgehog Proteins
  • Histones
  • Phosphoproteins
  • Smad Proteins
  • Smad4 Protein
  • Wnt Proteins
  • Xenopus Proteins
  • ihh protein, mouse
  • smad4.1 protein, Xenopus
  • Alkaline Phosphatase