The researchers found that inhibiting the enzyme PKR could prevent two processes central to the onset of arthritis: the production and activation of enzymes that break down connective tissue; and the release from cartilage of one of its principal constituents, proteoglycan.
They said: "Collectively these results support our hypothesis that PKR is implicated in the cartilage degradation that occurs in arthritic disease."
Despite the differences between osteoarthritis and rheumatoid arthritis, it is likely that similar molecular pathways can cause the degradation of cartilage in both diseases. Cartilage degradation results from an imbalance of enzymes that break down connective tissue and their inhibitors. In particular, activity levels of the enzymes MMP-2 and MMP-9 are frequently increased in the cartilage of people suffering from osteoarthritis.
The research team, led by Dr Sophie Gilbert, cultured cartilage cells in vitro. They then stimulated the cells with two molecules, TNF-a and C2-ceramide. The molecules simulated arthritic processes, increasing the release of proteoglycan and the production and activation of MMPs.
The researchers then repeated the experiment, but inhibited PKR at the same time. This time they found that there was no increase in the activation of MMP-2 or MMP9 and that the release of proteoglycan was significantly reduced.
Their results imply that PKR is involved in the molecular pathways, stimulated by TNF-a and C2-ceramide, that are implicated in the progression of arthritis, since the simulation of arthritis was prevented by inhibiting PKR.