Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype

Kevin Ngo, Prashanti Patil, Sara J. McGowan, Laura J. Niedernhofer, Paul D. Robbins, James Kang, Gwendolyn Sowa, Nam Vo

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1−/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss.

Original languageEnglish (US)
Pages (from-to)16-23
Number of pages8
JournalMechanisms of Ageing and Development
StatePublished - Sep 2017

Bibliographical note

Funding Information:
We would like to thank the Ferguson laboratory administrative and research staff for their support. The work was supported by the National Institute of Health ( AG044376 to NV and AG043376 to PDR and LJN). We would like to acknowledge the NIH supported microscopy resources in the Center for Biologic Imaging. Specifically the confocal microscope supported by grant number 1S10OD019973-01 .

Publisher Copyright:
© 2017


  • Aging
  • Cellular senescence
  • DNA damage
  • Intervertebral disc
  • Matrix proteoglycan


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