PUBLICATION

Ccn2a-FGFR1-SHH signaling is necessary for intervertebral disc homeostasis and regeneration in adult zebrafish

Authors
Rayrikar, A.Y., Wagh, G.A., Santra, M., Patra, C.
ID
ZDB-PUB-221203-3
Date
2022
Source
Development (Cambridge, England)   150(1): (Journal)
Registered Authors
Patra, Chinmoy, Rayrikar, Amey, Wagh, Ganesh
Keywords
CCN2, FGFR, Intervertebral disc, Regeneration, SHH, Zebrafish
MeSH Terms
  • Cell Communication
  • Intervertebral Disc*/metabolism
  • Signal Transduction/genetics
  • Receptor, Fibroblast Growth Factor, Type 1/genetics
  • Receptor, Fibroblast Growth Factor, Type 1/metabolism
  • Intervertebral Disc Degeneration*/genetics
  • Intervertebral Disc Degeneration*/metabolism
  • Intervertebral Disc Degeneration*/pathology
  • Adult
  • Aged
  • Animals
  • Nucleus Pulposus/metabolism
  • Nucleus Pulposus/pathology
  • Zebrafish*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Hedgehog Proteins/metabolism
  • Connective Tissue Growth Factor/genetics
  • Connective Tissue Growth Factor/metabolism
(all 19)
PubMed
36458546 Full text @ Development
Abstract
Intervertebral disc (IVD) degeneration is the primary cause of back pain in humans. However, the cellular and molecular pathogenesis of IVD degeneration is poorly understood. This study shows that zebrafish IVDs possess distinct and non-overlapping zones of cell proliferation and cell death. We find that in zebrafish, cellular communication network factor 2a (ccn2a) is expressed in notochord and IVDs. Although IVD development appears normal in ccn2a mutants, the adult mutant IVDs exhibit decreased cell proliferation and increased cell death leading to IVD degeneration. Moreover, Ccn2a overexpression promotes regeneration through accelerating cell proliferation and suppressing cell death in wild-type aged IVDs. Mechanistically, Ccn2a maintains IVD homeostasis and promotes IVD regeneration by enhancing outer annulus fibrosus cell proliferation and suppressing nucleus pulposus cell death through augmenting FGFR1-SHH signaling. These findings reveal that Ccn2a plays a central role in IVD homeostasis and regeneration, which could be exploited for therapeutic intervention in degenerated human discs.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ari1TgTransgenic Insertion
    ari2
      		Small Deletion
      bns50
        		Small Deletion
        pd3TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          ccn2bTALEN1-ccn2bTALEN
          1 - 1 of 1
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          Fish
          No data available
          Antibodies
          Name Type Antigen Genes Isotypes Host Organism
          Ab1-ctgfpolyclonal
            		IgGRabbit
            Ab1-mycmonoclonal
              		IgG1Mouse
              Ab1-shhapolyclonal
                		IgGRabbit
                1 - 3 of 3
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                Orthology
                No data available
                Engineered Foreign Genes
                Marker Marker Type Name
                DsRedEFGDsRed
                EGFPEFGEGFP
                1 - 2 of 2
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                Mapping
                No data available
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                Citation
                Rayrikar, A.Y., Wagh, G.A., Santra, M., Patra, C. (2022) Ccn2a-FGFR1-SHH signaling is necessary for intervertebral disc homeostasis and regeneration in adult zebrafish. Development (Cambridge, England). 150(1):.