Regulation of inflammation signalling by resveratrol in human chondrocytes in vitro

The inflammatory process plays a pivotal role during the pathogenesis of osteoarthritis, dominated by catabolic processes initiated by pro-inflammatory cytokines such as IL-1β. 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-1β in primary human articular chondrocytes treated with IL-1βin vitro. Resveratrol reversed significantly IL-1β-reduced cell proliferation and blocked IL-1β-stimulated cell membrane bound- and mature IL-1β synthesis in chondrocytes. Furthermore, resveratrol was able to inhibit the IL-1β-induced degradation of mitochondria and apoptosis in chondrocytes in a time-dependent manner. Because caspase inhibitor Z-DEVD-FMK abolished the IL-1β-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-1β-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-1β- (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.