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Dysregulation of STAT3 signaling is associated with endplate-oriented herniations of the intervertebral disc in Adgrg6 mutant mice.

Publication ,  Journal Article
Liu, Z; Easson, GWD; Zhao, J; Makki, N; Ahituv, N; Hilton, MJ; Tang, SY; Gray, RS
Published in: PLoS Genet
October 2019

Degenerative changes of the intervertebral disc (IVD) are a leading cause of disability affecting humans worldwide and has been attributed primarily to trauma and the accumulation of pathology during aging. While genetic defects have also been associated with disc degeneration, the precise mechanisms driving the initiation and progression of disease have remained elusive due to a paucity of genetic animal models. Here, we discuss a novel conditional mouse genetic model of endplate-oriented disc herniations in adult mice. Using conditional mouse genetics, we show increased mechanical stiffness and reveal dysregulation of typical gene expression profiles of the IVD in adhesion G-protein coupled receptor G6 (Adgrg6) mutant mice prior to the onset of endplate-oriented disc herniations in adult mice. We observed increased STAT3 activation prior to IVD defects and go on to demonstrate that treatment of Adgrg6 conditional mutant mice with a small molecule inhibitor of STAT3 activation ameliorates endplate-oriented herniations. These findings establish ADGRG6 and STAT3 as novel regulators of IVD endplate and growth plate integrity in the mouse, and implicate ADGRG6/STAT3 signaling as promising therapeutic targets for endplate-oriented disc degeneration.

Duke Scholars

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

October 2019

Volume

15

Issue

10

Start / End Page

e1008096

Location

United States

Related Subject Headings

  • Signal Transduction
  • STAT3 Transcription Factor
  • Receptors, G-Protein-Coupled
  • Mutation
  • Mice
  • Intervertebral Disc Displacement
  • Intervertebral Disc Degeneration
  • Intervertebral Disc
  • Humans
  • Growth Plate
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, Z., Easson, G. W. D., Zhao, J., Makki, N., Ahituv, N., Hilton, M. J., … Gray, R. S. (2019). Dysregulation of STAT3 signaling is associated with endplate-oriented herniations of the intervertebral disc in Adgrg6 mutant mice. PLoS Genet, 15(10), e1008096. https://doi.org/10.1371/journal.pgen.1008096
Liu, Zhaoyang, Garrett W. D. Easson, Jingjing Zhao, Nadja Makki, Nadav Ahituv, Matthew J. Hilton, Simon Y. Tang, and Ryan S. Gray. “Dysregulation of STAT3 signaling is associated with endplate-oriented herniations of the intervertebral disc in Adgrg6 mutant mice.PLoS Genet 15, no. 10 (October 2019): e1008096. https://doi.org/10.1371/journal.pgen.1008096.
Liu Z, Easson GWD, Zhao J, Makki N, Ahituv N, Hilton MJ, et al. Dysregulation of STAT3 signaling is associated with endplate-oriented herniations of the intervertebral disc in Adgrg6 mutant mice. PLoS Genet. 2019 Oct;15(10):e1008096.
Liu, Zhaoyang, et al. “Dysregulation of STAT3 signaling is associated with endplate-oriented herniations of the intervertebral disc in Adgrg6 mutant mice.PLoS Genet, vol. 15, no. 10, Oct. 2019, p. e1008096. Pubmed, doi:10.1371/journal.pgen.1008096.
Liu Z, Easson GWD, Zhao J, Makki N, Ahituv N, Hilton MJ, Tang SY, Gray RS. Dysregulation of STAT3 signaling is associated with endplate-oriented herniations of the intervertebral disc in Adgrg6 mutant mice. PLoS Genet. 2019 Oct;15(10):e1008096.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

October 2019

Volume

15

Issue

10

Start / End Page

e1008096

Location

United States

Related Subject Headings

  • Signal Transduction
  • STAT3 Transcription Factor
  • Receptors, G-Protein-Coupled
  • Mutation
  • Mice
  • Intervertebral Disc Displacement
  • Intervertebral Disc Degeneration
  • Intervertebral Disc
  • Humans
  • Growth Plate