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PLoS One. 2014 Jun 3;9(6):e98444. doi: 10.1371/journal.pone.0098444. eCollection 2014.

Wnt signaling activates Shh signaling in early postnatal intervertebral discs, and re-activates Shh signaling in old discs in the mouse.

Author information

1
Division of Orthopaedic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
2
The Perinatal Institute Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
3
Emeritus Professor, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
4
Tissue Engineering Regeneration and Repair Program, Hospital for Special Surgery, New York, New York, United States of America.

Abstract

Intervertebral discs (IVDs) are strong fibrocartilaginous joints that connect adjacent vertebrae of the spine. As discs age they become prone to failure, with neurological consequences that are often severe. Surgical repair of discs treats the result of the disease, which affects as many as one in seven people, rather than its cause. An ideal solution would be to repair degenerating discs using the mechanisms of their normal differentiation. However, these mechanisms are poorly understood. Using the mouse as a model, we previously showed that Shh signaling produced by nucleus pulposus cells activates the expression of differentiation markers, and cell proliferation, in the postnatal IVD. In the present study, we show that canonical Wnt signaling is required for the expression of Shh signaling targets in the IVD. We also show that Shh and canonical Wnt signaling pathways are down-regulated in adult IVDs. Furthermore, this down-regulation is reversible, since re-activation of the Wnt or Shh pathways in older discs can re-activate molecular markers of the IVD that are lost with age. These data suggest that biological treatments targeting Wnt and Shh signaling pathways may be feasible as a therapeutic for degenerative disc disease.

PMID:
24892825
PMCID:
PMC4043533
DOI:
10.1371/journal.pone.0098444
[Indexed for MEDLINE]
Free PMC Article

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