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


BACKGROUND
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.


CONCLUSIONS
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.
Division of Orthopaedic Surgery, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, Ohio 45229, USA.
Chitra Lekha
CL
Dahia
Eric J
EJ
Mahoney
Atiq A
AA
Durrani
Christopher
C
Wylie
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006132:Growth Plate / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007150:Immunohistochemistry; D008159:Lumbar Vertebrae / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D051901:Smad4 Protein; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism; D029867:Xenopus Proteins
D053823:Hedgehog Proteins; D006657:Histones; D010750:Phosphoproteins; D051785:Smad Proteins; D051901:Smad4 Protein; D051153:Wnt Proteins; D029867:Xenopus Proteins; C514061:ihh protein, mouse; C490808:smad4.1 protein, Xenopus; D000469:Alkaline Phosphatase