Isoliquiritigenin Inhibits IL-1β-Induced Production of Matrix Metalloproteinase in Articular Chondrocytes

Osteoarthritis (OA) is a major joint disease in which inflammatory cytokine interleukin-1 beta (IL-1 beta) and matrix metalloproteinases (MMPs) play a pivotal role. Isoliquiritigenin has been reported to have anti-inflammation activity. In this study, the effect of isoliquiritigenin on IL-1 beta-induced production of matrix metalloproteinase and nuclear factor kappa B (NF-kappa B) activation was analyzed. We treated primary cultured articular chondrocytes with isoliquiritigenin and the expressions of MMPs were analyzed on mRNA and protein level. The phosphorylation of I kappa Ba and p65 was analyzed to detect NF-kappa B activation. We also used in vivo model by treating mice with isoliquiritigenin and detecting the level of MMPs. IL-1 beta induced NF-kappa B activation and MMP-1, MMP-3, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 production on chondrocytes. A 10-mu M isoliquiritigenin treatment significantly inhibited IL-1 beta-induced NFkB activation and these MMPs production on chondrocytes. Injecting isoliquiritigenin into rat knee joint also inhibited IL-1 beta-induced NF-kappa B activation and MMPs production in articular cartilage. Isoliquiritigenin treatment inhibited IL-1 beta-induced MMPs production and NF-kappa B activation both in vitro and in vivo, suggesting a potential therapeutic role of isoliquiritigenin to treat osteoarthritis.