IL-1β promotes ADAMTS enzyme-mediated aggrecan degradation through NF-κB in human intervertebral disc

J Orthop Surg Res. 2015 Oct 6:10:159. doi: 10.1186/s13018-015-0296-3.

Abstract

Background: The purpose of this study is to investigate IL-1β regulation of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4 and ADAMTS-5) expression through nuclear factor kappa B (NF-κB) in human nucleus pulposus (NP) cells.

Methods: qRT-PCR and Western blot were used to measure ADAMTS expression. Transfections and gene silencing were used to determine the role of NF-κB on cytokine-mediated ADAMTS expression and its role in aggrecan degradation.

Results: IL-1β increased ADAMTS expression in NP cells. Treatment with NF-κB inhibitors abolished the inductive effect of the cytokines on ADAMTS expression. Silencing of p65 confirmed their role in IL-1β-dependent ADAMTS-4 and ADAMTS-5 expression and aggrecan degradation.

Conclusions: By controlling the activation of NF-κB signaling, IL-1β modulates the expression of ADAMTS in NP cells. To our knowledge, this is the first study that shows the contribution of both ADAMTS-4 and ADAMTS-5 to aggrecan degradation in human NP cells.

MeSH terms

  • ADAM Proteins / biosynthesis
  • ADAM Proteins / genetics
  • ADAM Proteins / physiology*
  • ADAMTS Proteins
  • ADAMTS4 Protein
  • Adult
  • Aggrecans / metabolism*
  • Cells, Cultured
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Silencing
  • Humans
  • Interleukin-1beta / pharmacology
  • Interleukin-1beta / physiology*
  • Intervertebral Disc / cytology
  • Intervertebral Disc / metabolism*
  • Middle Aged
  • NF-kappa B / physiology
  • Procollagen N-Endopeptidase / biosynthesis
  • Procollagen N-Endopeptidase / genetics
  • Procollagen N-Endopeptidase / physiology*
  • Signal Transduction / drug effects
  • Transcription Factor RelA / biosynthesis
  • Transcription Factor RelA / genetics
  • Young Adult

Substances

  • Aggrecans
  • Interleukin-1beta
  • NF-kappa B
  • Transcription Factor RelA
  • ADAM Proteins
  • ADAMTS Proteins
  • ADAMTSL5 protein, human
  • Procollagen N-Endopeptidase
  • ADAMTS4 Protein
  • ADAMTS4 protein, human