Regulation of type II collagen, matrix metalloproteinase-13 and cell proliferation by interleukin-1β is mediated by curcumin via inhibition of NF-κB signaling in rat chondrocytes

Curcumin possesses strong anti-inflammatory, anti-rheumatoid and anti-oxidative activities, and has the potential to inhibit nuclear factor-kappa B (NF-kappa B) signaling. Cartilage damage in osteoarthritis (OA) is largely mediated by interleukin-1 beta (IL-1 beta) via activation of various transcription factors, including NF-kappa B and activator protein-1. The aim of the present study was to determine whether IL-1 beta induces matrix metalloproteinase-13 (MMP-13) expression and inhibits type II collagen expression, as well as to examine whether cell proliferation may be inhibited by curcumin through the inhibition of NF-kappa B signaling. The effects of curcumin were investigated in rat articular chondrocyte cell cultures treated with IL-1 beta in the presence or absence of curcumin or the NF-kappa B inhibitor pyrrolidine dithiocarbamate. Western blotting and reverse transcription-quantitative polymerase chain reaction were conducted to evaluate protein and mRNA expression levels of type II collagen, MMP-13, NF-kappa B inhibitor a (I kappa B alpha), phosphorylated-I kappa B alpha and NF-kappa B subunit p65/RelA. Western blotting and immunofluorescence were performed to examine the effects of curcumin on the expression, phosphorylation and nuclear translocation of NF-kappa B-associated proteins. The effects of curcumin on cell proliferation were evaluated by Cell Counting Kit-8 (CCK-8). Curcumin was demonstrated to inhibit the IL-1 beta-induced activation of NF-kappa B by suppressing I kappa B alpha phosphorylation and p65/RelA nuclear translocation. These events were associated with the downregulation of MMP-13 expression and the upregulation of type II collagen expression, both of which are considered to be NF-kappa B targets. CCK-8 assays revealed that co-treatment with curcumin resulted in increased proliferation in IL-1 beta-treated chondrocytes. These findings implicated curcumin as a naturally occurring anti-inflammatory agent for the treatment of OA via inhibition of NF-kappa B signaling.