New Pathway to Onset of Arthritis Identified
Study targets enzymes that break down tissue and cartilage
FRIDAY, Nov. 14, 2003 (HealthDayNews) -- British researchers say they have discovered a way to block a molecular mechanism that triggers arthritis, and they claim their finding could lead to new drugs for the joint disease.
Working with cultured cartilage cells, the scientists found blocking the enzyme protein kinase R (PKR) stopped the production of enzymes that break down connective tissue and allow proteoglycan, a basic component of cartilage, to be lost.
"We found that treating cartilage cells with tumor necrosis factor-alpha (TNF-alpha) and C2-ceramide simulated the arthritic processes by a number of mechanisms," says lead researcher Dr. Sophie Gilbert, a connective tissue expert from the School of Biosciences at Cardiff University. Specifically, Gilbert and her colleagues saw an increase in the release of matrix metalloproteinase (MMP-2 and -9), two enzymes involved in arthritis.
Treatment of the cartilage cells with TNF-alpha and C2-ceramide also led to an increased loss of proteoglycans, and "we also saw increased cartilage cell death," Gilbert adds.
"Our results suggest that ceramide may help TNF-alpha signaling in cartilage. These effects were blocked by treatment of cartilage with 2-aminopurine, an inhibitor of the PKR, which has not previously been linked to ceramide signaling in cartilage," she says.
"This study confirms that a new intracellular signaling pathway involving PKR is important in cartilage degradation," she says. Through understanding these basic mechanisms underlying arthritis, studies such as this may lead to the discovery of new arthritis drugs, Gilbert adds.
The study appears in the current online issue of Arthritis Research and Therapy.
"Since arthritis is a significant cost to health care, financially and in human suffering, it is essential to identify mechanisms of disease onset so that intervention and diagnosis can be achieved before debilitating cartilage loss. This study goes some way to achieving this goal," she says.
Dr. John Klippel, president and chief executive officer of the Arthritis Foundation, comments that "cartilage destruction occurs in both rheumatoid and osteoarthritis, and this study shows that PKR has an important role in activating enzymes that are known to cause joint damage in both diseases."
"So PKR appears to be a target for developing drugs that can prevent cartilage damage and limit the risk of disability from arthritis," he adds.
To learn more about arthritis, visit the National Institute of Arthritis and Musculoskeletal and Skin Diseases or the Arthritis Foundation.