ENZYME INVOLVED IN ARTHRITIS ONSET UNCOVERED

Enzyme involved in arthritis onset uncovered

ANI
Wednesday, November 12, 2003
 
Washington - Researchers at Cardiff University have
uncovered a molecular pathway that plays a pivotal role
in the onset of arthritis. 

The research, published in the latest issue of Arthritis
Research and Therapy , could aid in the discovery of
novel targets for arthritis drugs. 

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. 

"Collectively these results support our hypothesis that
PKR is implicated in the cartilage degradation that
occurs in arthritic disease," the researchers said. 

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 MMP-9
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. 

http://timesofindia.indiatimes.com/cms.dll/articleshow?msid=280016

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