Intercellular signaling pathways active during intervertebral disc growth, differentiation, and aging.
METHODS
Intervertebral discs at different postnatal ages were assessed for active intercellular signaling pathways.


OBJECTIVE
To generate a spatial and temporal map of the signaling pathways active in the postnatal intervertebral disc (IVD).


BACKGROUND
The postnatal IVD is a complex structure, consisting of 3 histologically distinct components, the nucleus pulposus, fibrous anulus fibrosus, and endplate. These differentiate and grow during the first 9 weeks of age in the mouse. Identification of the major signaling pathways active during and after the growth and differentiation period will allow functional analysis using mouse genetics and identify targets for therapy for individual components of the disc.


METHODS
Antibodies specific for individual cell signaling pathways were used on cryostat sections of IVD at different postnatal ages to identify which components of the IVD were responding to major classes of intercellular signal, including sonic hedgehog, Wnt, TGFbeta, FGF, and BMPs.


RESULTS
We present a spatial/temporal map of these signaling pathways during growth, differentiation, and aging of the disc.


CONCLUSIONS
During growth and differentiation of the disc, its different components respond at different times to different intercellular signaling ligands. Most of these are dramatically downregulated at the end of disc growth.
Dahia
Chitra Lekha
CL
Division of Orthopaedic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Mahoney
Eric J
EJ
Durrani
Atiq A
AA
Wylie
Christopher
C
D000375:Aging / Q000502:physiology*; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006132:Growth Plate / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D044162:Parathyroid Hormone-Related Protein; C465570:Shh protein, mouse; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D005346:Fibroblast Growth Factors