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.

Abstract

Curcumin possesses strong anti-inflammatory, anti-rheumatoid and anti-oxidative activities, and has the potential to inhibit nuclear factor-κB (NF-κB) signaling. Cartilage damage in osteoarthritis (OA) is largely mediated by interleukin-1β (IL-1β) via activation of various transcription factors, including NF-κB and activator protein-1. The aim of the present study was to determine whether IL-1β 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-κB signaling. The effects of curcumin were investigated in rat articular chondrocyte cell cultures treated with IL-1β in the presence or absence of curcumin or the NF-κB 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-κB inhibitor α (IκBα), phosphorylated-IκBα and NF-κB subunit p65/RelA. Western blotting and immunofluorescence were performed to examine the effects of curcumin on the expression, phosphorylation and nuclear translocation of NF-κB-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-1β-induced activation of NF-κB by suppressing IκBα 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-κB targets. CCK-8 assays revealed that co-treatment with curcumin resulted in increased proliferation in IL-1β-treated chondrocytes. These findings implicated curcumin as a naturally occurring anti-inflammatory agent for the treatment of OA via inhibition of NF-κB signaling.