Regulation of inflammation signalling by resveratrol in human chondrocytes in vitro

Biochem Pharmacol. 2008 Feb 1;75(3):677-87. doi: 10.1016/j.bcp.2007.09.014. Epub 2007 Sep 18.


The inflammatory process plays a pivotal role during the pathogenesis of osteoarthritis, dominated by catabolic processes initiated by pro-inflammatory cytokines such as IL-1beta. Resveratrol, a natural phytoalexin occurring in various fruits has previously been shown to exhibit anti-inflammatory properties in several cell types. We investigated, whether resveratrol may be a useful blocker of pro-inflammatory cytokine signalling pathways in arthritis. We first examined the effects of resveratrol on the proliferation and production of IL-1beta in primary human articular chondrocytes treated with IL-1betain vitro. Resveratrol reversed significantly IL-1beta-reduced cell proliferation and blocked IL-1beta-stimulated cell membrane bound- and mature IL-1beta synthesis in chondrocytes. Furthermore, resveratrol was able to inhibit the IL-1beta-induced degradation of mitochondria and apoptosis in chondrocytes in a time-dependent manner. Because caspase inhibitor Z-DEVD-FMK abolished the IL-1beta-induced apoptosis in chondrocytes, we examined the effect of resveratrol on the caspase pathway and found that resveratrol blocked the cysteine protease caspase-3 and subsequent cleavage of the DNA repair enzyme PARP. Additionally, resveratrol reversed the IL-1beta-induced up-regulation of reactive oxygen species (ROS) in chondrocytes. Finally, we show that resveratrol induced ubiquitin-independent degradation of tumor suppressor gene protein p53 and inhibited p53-induced apoptosis in chondrocytes in a dose-dependent manner. Our results indicate that resveratrol seems to be an effective in vitro anti-inflammatory agent and has a chondroprotective capacity through suppression of (1) IL-1beta- (2) ROS- and (3) tumor suppressor protein p53-production. Further studies should be undertaken to define a possible implication of resveratrol in osteoarthritis therapy and cartilage tissue engineering.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Humans
  • Interleukin-1beta / pharmacology
  • Poly(ADP-ribose) Polymerases / metabolism
  • Resveratrol
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Stilbenes / pharmacology*
  • Tumor Suppressor Protein p53 / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-1beta
  • Stilbenes
  • Tumor Suppressor Protein p53
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • Resveratrol