Arthritis Clues Found in New Studies

< Dec. 7, 2005 > -- Adding another piece to the rheumatoid arthritis puzzle, a team of researchers believe they have discovered the role a key protein plays in the painful inflammatory joint condition, according to a report in the medical journal Arthritis and Rheumatism.

A chronic, painful, and often disabling autoimmune disease that affects more than 2 million Americans, rheumatoid arthritis is defined by severe inflammation of the lining of the joints.

This inflammation leads to a slow degeneration of bone and cartilage over time. According to the Arthritis Foundation, women are two to three times more likely to be stricken with the illness then men.

The average onset for rheumatoid arthritis, the most crippling form of arthritis, is between the ages of 20 and 45 years old.

The protein studied by the researchers, Type II Collagen (CII), appears change at the onset of rheumatoid arthritis (RA). It then morphs into a destructive anti-immunity weapon that weakens the body's immune system while promoting the chronic inflammation of joints.

Research Offers Better Understanding

The finding might someday point to new drug targets against the disease, the scientists said.

"Our study has important implications for the further study and enhanced understanding of the pathology of RA," says study author Dr. Ahuva Nissim, of the Queen Mary's School of Medicine and Dentistry at the University of London.

Dr. Nissim set out to better understand the disease, which to date has no clear cause and no known cure.

To do so, they honed in on RA's effect on Type II Collagen (CII) - a major protein component of cartilage, bone, and tendons.

The team theorized that CII - normally a key player in healthy joint function - might also help spur RA when stressed by inflammation.

They found that when inflammatory cells enter joint tissue they over-consume oxygen. In turn, oxygen depletion undercuts the function of otherwise healthy proteins by modifying them in such a way as to encourage binding with sugar molecules.

This binding further encourages inflammation. The result: a vicious biochemical cycle that results in chronic RA pain.

To determine whether CCII was, in fact, one of the principle culprits in this process, the researchers first obtained blood serum samples from 31 male and female RA patients between the ages of 65 and 93.

Blood specimens were also taken from 41 patients suffering from other inflammatory joint diseases, such as back pain, osteoporosis, and gout.

All the samples were exposed to normal CII protein taken from cows, as well as CII modified with one of three oxidants or a common sugar - all of which are present during the inflammation typically found in a rheumatic joint.

The authors say the normal form of the CII protein rarely bound with antibodies from blood samples taken from RA patients.

However, 45 percent of the RA blood samples showed evidence of antibody binding when exposed to the altered form of the protein. In fact, the binding rate was four times higher than that seen with non-modified CII. Modified CII did not bind as often with blood drawn from non-RA patients, they add.

Based on these findings, the researchers believe RA alters CII proteins to further upset the immune response and perpetuate the disease.

Hope for New Therapies

According to the researchers, these early results could lead to practical treatment benefits, both through new clinical insights into how RA works and by highlighting novel targets for intervention.

"In the future, understanding of this process will help us develop specific therapeutics which will target only the inflamed joints," remarks Dr. Nissim.

Dr. Stephen Lindsey, head of rheumatology at Ochsner Clinic Foundation Hospital in Baton Rouge, La., says, "It's a promising avenue of research in trying to develop further what's making RA such a chronic disease. They're looking at why the body forms immunological reactions against itself, which it's not supposed to do.

“But I think it's interesting, more than it is leading to any promise of new therapies," he adds.

Second Study Looks at Osteoarthritis

Regular physical activity may strengthen knee cartilage, states another new study reported in Arthritis and Rheumatism.

Osteoarthritis (OA) is the leading cause of disability among adults. Approximately 20.7 million adults in the US have the most common form of arthritis, osteoarthritis, also called degenerative joint disease. Most persons over the age of 65 are affected with osteoarthritis in at least one joint, making this condition a leading cause of disability in the US.

Along with early diagnosis, moderate exercise is one of the most effective ways to reduce pain and improve function in patients with OA of the knee and hip. Yet, more than 60 percent of U.S. adults with arthritis fail to meet the minimum recommendations for physical activity.

Based on the "wear and tear" nature of OA, the commonly held belief is that exercise will not strengthen joint cartilage and may even aggravate cartilage loss.

Until recently, investigators were unable to put that belief to the test. Radiographs (x-rays), the standard measure of OA's progression, made it impossible to assess cartilage before severe cartilage damage had occurred.

Advances in magnetic resonance imaging (MRI) now make it possible to study cartilage changes earlier in the course of OA. Two researchers in Sweden, Dr. Leif Dahlberg and Ewa M. Roos, P.T., Ph.D., used a novel MRI technique to look at the impact of moderate exercise on the knee cartilage and found therapeutic value in exercise.

The researchers recruited 29 men and 16 women, between the ages of 35 and 50, who had undergone meniscus (a type of cartilage in the knee) repair within the past 3 to 5 years. Subjects were randomly assigned to either an exercise group or a control group.

The exercise group was enrolled in a supervised program of aerobic and weight-bearing moves, for one hour, three times weekly for four months.

At the study's onset and follow-up, subjects from both groups underwent MRI scans to evaluate knee cartilage. The technique used focused specifically on the cartilage's glycosaminoglycan (GAG) content, a key component of cartilage strength and elasticity.

Subjects also answered a series of questions about their knee pain and stiffness, as well as their general activity level.

In the exercise group, many subjects reported gains in physical activity and functional performance tests compared with subjects in the control group. Improvements in tests of aerobic capacity and stamina affirmed the self-reported changes.

In addition, MRI measures of the GAG content showed a strong correlation with the increased physical training of the subjects who had regularly participated in moderate, supervised exercise.

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