Small molecule inhibitors block interleukin 1β (IL-1β)/tumor necrosis factor α (TNFα)-induced expression of matrix metalloproteinases without affecting the IL-1β/TNFα-induced decrease in mRNA expression of cartilage markers. (A) Significant upregulation of Mmp3 expression was found when metatarsals were treated with IL-1β and TNFα. Both PKF115-584 and CGP049090 decreased this upregulation after 4 days of cotreatment, whereas PKF118-310 did not have an effect. Mmp9 expression was significantly downregulated by PKF115-584 after 1 day and IL-1β/TNFα-induced upregulation was prevented by both PKF115-584 and CGP049090, but not by PKF118-310, after 4 days of culture. Expression of Mmp13 was significantly upregulated by IL-1β and TNFα, whereas this effect was blocked by cotreatment with PKF115-584 or CGP049090, but not with PKF118-310. MMP, matrix metalloproteinase. (B) Acan expression is significantly decreased by IL-1β and TNFα at both day 1 and day 4. Also, small molecules PKF115-584 and CGP049090 downregulated expression of Acan by themselves. Expression of Col2a1 is downregulated by IL-1β and TNFα, and this effect could not be counteracted by small molecules. No significant effects on Sox9 expression were found. Data represent the means of two independent experiments with 95% confidence intervals. *P < 0.05.
Landman et al. Arthritis Research & Therapy 2013 15:R93 doi:10.1186/ar4273