Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

Exp Cell Res. 2017 Mar 15;352(2):322-332. doi: 10.1016/j.yexcr.2017.02.023. Epub 2017 Feb 16.

Abstract

Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity.

Keywords: Extracellular matrix; Intervertebral disc degeneration; Matrix metalloproteinase; Nuclear factor-κB; Sirtuin 6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Cells, Cultured
  • Extracellular Matrix / metabolism*
  • Female
  • Humans
  • Intervertebral Disc Degeneration / metabolism*
  • Intervertebral Disc Degeneration / pathology
  • Male
  • Middle Aged
  • NF-kappa B / metabolism*
  • Nucleus Pulposus / metabolism
  • Nucleus Pulposus / pathology
  • Protein Binding
  • Signal Transduction
  • Sirtuins / genetics
  • Sirtuins / metabolism*

Substances

  • NF-kappa B
  • SIRT6 protein, human
  • Sirtuins