Scientists at OMRF have found a novel cellular process that contributes to the development of osteoarthritis. The discovery could lead to new treatments for the most common form of arthritis.
Osteoarthritis affects roughly 27 million Americans, according to the Arthritis Foundation. It occurs when the cartilage that cushions bones at the joints breaks down and wears away, allowing the bones to rub against one another. It can strike any joint, but it’s most common in the knees, hips, lower back, neck and fingers.
With age, cartilage oxidizes, a process that is caused by the creation of free radicals—highly reactive oxygen molecules. The build-up of these molecules is thought to damage the cartilage and contribute to the development of osteoarthritis.
In the new study, OMRF researchers Tim Griffin, Ph.D., and Yao Fu, Ph.D., looked at the effect of aging on the levels of cellular antioxidants, substances that block the action of those free radicals. Specifically, they wanted to know if aging increases the risk of osteoarthritis by reducing antioxidants that slow or alleviate cellular damage in the knee cartilage of aging rats.
While the scientists found that the rodents’ cartilage maintained the levels of most antioxidants, one particular antioxidant enzyme (known as SOD2) increased as the rats aged. But the actual function of SOD2 declined as the rodents grew older and did not seem to combat the cellular damage caused by the free radicals.
“It would be like calling in the fire department and half of them arriving on the scene without hoses,” said Griffin. “They’re there, but they’re not able to put out the fire.”
Further study showed that SOD2 had undergone an extra chemical modification, called acetylation. This change was the trigger that limited its activity.
“No one had ever shown this particular change in the context of osteoarthritis,” said Griffin.
When the OMRF researchers added another protein (called SIRT3) in the lab, this revitalized the activity of the SOD2 enzyme by removing the chemical modification. The scientists also observed these changes in osteoarthritic cartilage obtained from patients undergoing joint replacement therapy. As a result, Griffin and Fu believe that reactivating or promoting SIRT3 may help reduce the oxidative stress that occurs during the development of osteoarthritis.
“We think a change occurs in how these cells make energy to perform their basic cellular functions,” said Fu. “That seems to change the chemical environment that reduces the function of SOD2.”
Griffin said the findings could lead to new therapies for the joints. “Drugs used for other metabolic diseases like diabetes or even cancer might have some therapeutic potential for osteoarthritis.”
Griffin and Fu have published their findings in the journal Arthritis and Rheumatology. Funding for the research was provided by grants from the National Institutes of Health (grant numbers P30-AR-053483, P20-RR-018758, P20-GM-103441, R01-AG-049058, P20-GM-104934) and the Arthritis Foundation.
