Regulation of type II collagen, matrix metalloproteinase-13 and cell proliferation by interleukin-1ß 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 factor­κB (NF­κB) signaling. Cartilage damage in osteoarthritis (OA) is largely mediated by interleukin-1ß (IL-1ß) via activation of various transcription factors, including NF­κB and activator protein­1. The aim of the present study was to determine whether IL­1ß 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 NF­κB signaling. The effects of curcumin were investigated in rat articular chondrocyte cell cultures treated with IL­1ß in the presence or absence of curcumin or the NF­κB inhibitor pyrrolidine dithiocarbamate. Western blotting and reverse transcription­quantitative polymerase chain reaction were conducted to evaluate protein and mRNA expression levels of type II collagen, MMP­13, NF­κB inhibitor α (IκBα), phosphorylated­IκBα and NF­κB subunit p65/RelA. Western blotting and immunofluorescence were performed to examine the effects of curcumin on the expression, phosphorylation and nuclear translocation of NF­κB­associated proteins. The effects of curcumin on cell proliferation were evaluated by Cell Counting Kit­8 (CCK­8). Curcumin was demonstrated to inhibit the IL­1ß­induced activation of NF­κB by suppressing IκBα phosphorylation and p65/RelA nuclear translocation. These events were associated with the downregulation of MMP­13 expression and the upregulation of type II collagen expression, both of which are considered to be NF­κB targets. CCK­8 assays revealed that co­treatment with curcumin resulted in increased proliferation in IL­1ß­treated chondrocytes. These findings implicated curcumin as a naturally occurring anti­inflammatory agent for the treatment of OA via inhibition of NF­κB signaling.