Interleukin-1 inhibits Sox9 and collagen type II expression via nuclear factor-kappaB in the cultured human intervertebral disc cells

Chin Med J (Engl). 2009 Oct 20;122(20):2483-8.

Abstract

Background: The most significant biological change in intervertebral disc degeneration is the decrease of chondrocyte specific gene and protein expression of Sox9 and collagen type II. Interleukin-1 (IL-1) is not expressed in the normal intervertebral disc tissue but increases in the degenerated intervertebral disc tissue. This suggests that IL-1 may play a role in regulation of the expression of Sox9 and collagen type II.

Methods: Human intervertebral disc cells were isolated and cultured. Sox9 and collagen type II expression during treatment with IL-1, with or without the nuclear factor-kappaB (NF-kappaB) activity inhibitor curcumin, were detected by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, and the activity of the NF-kappaB signaling pathway was detected by the electrophoretic mobility shift assay (EMSA).

Results: IL-1 lowered the mRNA level and protein expression of Sox9 and collagen type II in the cultured intervertebral disc cells in a dose dependent manner (P < 0.05), and this effect was attenuated by curcumin. Curcumin alone had no effect on Sox9 and collagen type II expression (P > 0.05). IL-1 at concentrations of 0.1 ng/ml, 1 ng/ml and 10 ng/ml could stimulate the activity of NF-kappaB in the intervertebral disc cells in a dose dependent manner (P < 0.05) that was inhibited by curcumin.

Conclusions: We demonstrated the previously unknown function of IL-1 in inhibiting Sox9 and collagen type II via NF-kappaB in the intervertebral disc cells. This inhibition can be attenuated by curcumin, which is an effective NF-kappaB activity inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Collagen Type II / genetics
  • Collagen Type II / metabolism*
  • Curcumin / pharmacology*
  • Electrophoretic Mobility Shift Assay
  • Gene Expression / drug effects
  • Humans
  • Immunoblotting
  • Interleukin-1 / pharmacology*
  • Intervertebral Disc / cytology*
  • Male
  • NF-kappa B / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism*

Substances

  • Collagen Type II
  • Interleukin-1
  • NF-kappa B
  • SOX9 Transcription Factor
  • Curcumin