Inhibition of protein kinase C does not prevent reduction in levels of aggrecan or type II collagen mRNA by tumor necrosis factor alpha (TNF-α) and epidermal growth factor (EGF). Confluent monolayers of chondrocytes were pretreated with 10 μm bisindolylmaleimide (BIS) I or the structurally related, nonfunctional analog BIS V (10 μm) for 15 min, followed by treatment with TNF-α (30 ng/ml), EGF (10 ng/ml) or TNF-α + EGF in combination for 24 hours. Levels of (a) aggrecan and (b) type II collagen mRNA were determined by northern blot analysis of total RNA (10 μg). Levels were normalized to levels of 18S rRNA and data are expressed as the percentage of respective controls ± standard error of the mean (n = 4–6). a Significant difference from respective control populations (P < 0.05), b significant difference from populations treated individually with TNF-α or EGF (P < 0.001).