Inhibition of hydrogen peroxide, lipopolysaccharide and interleukin-1 beta-induced prostaglandin E-2 production in chondrocytes by the combination of avocado/soybean unsaponifiables and lipoic acid

Abstract

s / Osteoarthritis and Cartilage 20 (2012) S54–S296 S241 Purpose: Rheumatoid arthritis (RA) synoviocytes present an increased mitochondrial genome mutagenesis, leading to mitochondrial alterations that might be participating in the pathogenesis of the disease. This study was performed to examine whether mitochondrial dysfunction is involved in joint destruction and inflammation in RA in relation to the expression of matrix metalloproteinases-1 and -3 (MMP-1 and MMP-3) and vascular endothelial growth factor (VEGF) in normal human synoviocytes. Methods: Normal human synoviocytes were treated with the commonly usedmitochondrial respiratory inhibitor oligomycin (OLI) (10 mg/ml) for 24 hours. As a positive control, MMPs and VEGF expression was induced by 5ng/ml interleukin-1b (IL-1b). MMPs and VEGFmRNA expression (RT-PCR) and MMP-1 protein levels (ELISA) were analyzed. The effect of the natural antioxidant resveratrol (RSV, 50 mM) was tested. Results: We found that oligomycin-induced mitochondrial dysfunction in synoviocytes for 24h significantly increased MMP-1 mRNA expression (835,7 480,4 vs. Basal 1, n1⁄46, p<0.05), evenmore than higher levels of the positive control IL-1b (580,3 343,2). This increase in MMP-1 mRNA expression was accompanied by the synthesis of MMP-1 protein (702