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Cell type-specific effects of Notch signaling activation on intervertebral discs: Implications for intervertebral disc degeneration.

Publication ,  Journal Article
Zheng, Y; Liu, C; Ni, L; Liu, Z; Mirando, AJ; Lin, J; Saijilafu, ; Chen, D; Hilton, MJ; Li, B; Chen, J
Published in: J Cell Physiol
July 2018

Intervertebral disc (IVD) degeneration is the major cause of back pain. Notch signaling is activated in annulus fibrosus (AF) and nucleus pulposus (NP) tissues of degenerated IVDs, and induced by IL1-β and TNF-α in NP cells. However, the role of Notch activatin in the pathogenesis of IVD degeneration is largely unknown. In this study, we overexpressed the Notch1 intracellular domain (NICD1) in AF, NP, and chondrogenic ATDC5 cells via adenoviruses. Overexpression of NICD1 activated transcription of Notch signaling target genes in AF, NP, and ATDC5 cells, and caused cell type-specific effects on expression of matrix anabolic and catabolic genes. Activation of Notch signaling promoted expression of matrix catabolic genes and inhibited expression of matrix anabolic genes in both AF and ATDC5 cells, whereas its activation suppressed expression of matrix catabolic genes (including Mmp3, Mmp13, Adamts4, and Adamts5) and attenuated TNF-α and inflammatory macrophage-induced Mmp13 expression in NP cells. Consistently, sustained activation of Notch1 signaling in postnatal IVDs in mice severely disrupted growth plate and endplate cartilage tissues, but did not overly affect NP tissues. Together, these data indicated that activation of Notch signaling exerted differential and cell type-specific effects in intervertebral discs, and specific Notch signaling regulation may be considered during the treatment of IVD degeneration.

Duke Scholars

Published In

J Cell Physiol

DOI

EISSN

1097-4652

Publication Date

July 2018

Volume

233

Issue

7

Start / End Page

5431 / 5440

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Signal Transduction
  • Receptors, Notch
  • Receptor, Notch1
  • Rats
  • Nucleus Pulposus
  • Mice
  • Macrophages
  • Intervertebral Disc Degeneration
  • Intervertebral Disc
 

Citation

APA
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Zheng, Y., Liu, C., Ni, L., Liu, Z., Mirando, A. J., Lin, J., … Chen, J. (2018). Cell type-specific effects of Notch signaling activation on intervertebral discs: Implications for intervertebral disc degeneration. J Cell Physiol, 233(7), 5431–5440. https://doi.org/10.1002/jcp.26385
Zheng, Yixin, Cunchang Liu, Li Ni, Zhaoyang Liu, Anthony J. Mirando, Jun Lin, Jun Saijilafu, et al. “Cell type-specific effects of Notch signaling activation on intervertebral discs: Implications for intervertebral disc degeneration.J Cell Physiol 233, no. 7 (July 2018): 5431–40. https://doi.org/10.1002/jcp.26385.
Zheng Y, Liu C, Ni L, Liu Z, Mirando AJ, Lin J, et al. Cell type-specific effects of Notch signaling activation on intervertebral discs: Implications for intervertebral disc degeneration. J Cell Physiol. 2018 Jul;233(7):5431–40.
Zheng, Yixin, et al. “Cell type-specific effects of Notch signaling activation on intervertebral discs: Implications for intervertebral disc degeneration.J Cell Physiol, vol. 233, no. 7, July 2018, pp. 5431–40. Pubmed, doi:10.1002/jcp.26385.
Zheng Y, Liu C, Ni L, Liu Z, Mirando AJ, Lin J, Saijilafu, Chen D, Hilton MJ, Li B, Chen J. Cell type-specific effects of Notch signaling activation on intervertebral discs: Implications for intervertebral disc degeneration. J Cell Physiol. 2018 Jul;233(7):5431–5440.
Journal cover image

Published In

J Cell Physiol

DOI

EISSN

1097-4652

Publication Date

July 2018

Volume

233

Issue

7

Start / End Page

5431 / 5440

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Signal Transduction
  • Receptors, Notch
  • Receptor, Notch1
  • Rats
  • Nucleus Pulposus
  • Mice
  • Macrophages
  • Intervertebral Disc Degeneration
  • Intervertebral Disc