Resveratrol regulates type II collagen and COX-2 expression via the ERK, p38 and Akt signaling pathways in rabbit articular chondrocytes

Resveratrol, a naturally occurring polyphenolic phytoalexin antioxidant compound present in grapes and red wine, has been reported to induce various biochemical responses. It has been shown to possess anti-aging, anti-inflammatory and anti-proliferative activities in several cell types. However, the effects of resveratrol in normal cells, including chondrocytes, have not yet been clearly elucidated. The aim of the present study was to evaluate the effects of resveratrol on differentiation and inflammation in rabbit articular chondrocytes and to investigate the underlying mechanism of action. Rabbit articular chondrocytes were treated with 20 μM resveratrol for different time periods or with various concentrations of resveratrol for 24 h. It was observed that the expression levels of type II collagen and sulfated proteoglycan, as determined by western blot analysis and Alcian blue staining, respectively, increased following treatment with resveratrol in a concentration-dependent manner at concentrations up to 20 μM and then decreased at higher concentrations. The expression levels of cyclooxygenase (COX-2) and prostaglandin E₂ (PGE₂) began to increase at 10 min after the addition of resveratrol, reached peak levels at 3 h and decreased from the peak level thereafter, as determined by western blot analysis and PGE₂ assay, respectively. It was also demonstrated that resveratrol caused phosphorylation of mitogen-activated protein kinase proteins [extracellular signal-regulated kinases (ERK), p38 and c-Jun N-terminal kinases (JNK)] and Akt in rabbit articular chondrocytes. The inhibition of ERK, p38 kinase, phosphoinositide 3-kinase (PI3K) and Akt with PD98059, SB203580, LY294002 and triciribine, respectively, suppressed resveratrol-induced type II collagen and COX-2 expression. However, inhibition of JNK with SP600125 produced no clear changes in the expression levels of type II collagen and COX-2. The results suggest that resveratrol in articular chondrocytes stimulates differentiation and inflammation via the ERK, p38 and Akt signaling pathways.