April 03, 2013
By David Martin
|Jinxi Wang, M.D., Ph.D.|
Osteoarthritis — the most common form of arthritis — affects an estimated 27 million Americans. Often called wear-and-tear arthritis, osteoarthritis breaks down cartilage, the tough but flexible tissue that cushions joint surfaces. When joint pain is described as "bone on bone," osteoarthritis is usually at fault. The disease typically occurs in individuals who are 45 and older, is more common in women than in men, and usually affects joints in the hands, neck, lower back, knees and hips. Doctors currently treat the symptoms of osteoarthritis by prescribing rest, physical therapy, pain medicine or joint injections of corticosteroid or other medications. Joint replacement surgery is also an option for patients with late-stage osteoarthritis.
Now a medical scientist at the University of Kansas Medical Center has identified a link between a protein and osteoarthritis. The protein forms the basis of a patent for a potential new method of preventing and treating the disease.
"Pain medicines may bring relief for the short term," Jinxi Wang, M.D., Ph.D, says of current treatments, "but it's not going to cure the disease."
Wang is the Mary Alice and Paul R. Harrington Distinguished Professor of Orthopedics and the director of the Harrington Laboratory for Molecular Orthopedics at KU Medical Center. The two main research programs in his lab are bone repair and osteoarthritis.
Wang says there are several reasons why it has been difficult to make progress in the fight against osteoarthritis. For one thing, scientists are unsure what causes it. Joint injury or abnormal alignment might predispose an individual to osteoarthritis, though some forms of it appear to be hereditary. Hormones also appear to play a role.
In any case, the molecular and cellular mechanisms of osteoarthritis remain unclear. Previous studies have suggested that some enzymes and inflammatory proteins may cause cartilage breakdown. However, no anti-osteoarthritis drug candidate targeting a single inflammatory protein or degrading enzyme have proven effective in clinical trials.
Establishing metabolic balance
Wang and his team in the Harrington lab have looked for answers in metabolism, the sum of the chemical processes by which cells produce the materials and energy necessary for life. "To cure or prevent disease, you need to know molecular medicine," he says. Individuals with osteoarthritis have an imbalance in the metabolism of their joint cartilage and surrounding tissues. There is too much catabolism, or tearing down, and not enough anabolism for repair, or building up.
"We want to find a good metabolic balance in joint tissues," Wang says.
Wang and his collaborators have identified a protein that may play a role in maintaining the balance. His research group discovered that mice lacking the Nfat1 protein displayed changes in major weight-bearing joints — hip, knee, shoulder — including the loss of cartilage and bone changes such as the formation of bone spurs. The changes looked very similar to the osteoarthritis changes seen in humans.
For Wang, the next step is to determine the extent to which Nfat1 deficiency is associated with osteoarthritis in humans. Using blood and joint tissue surgeons have removed, he has determined that a substantial percentage of osteoarthritis patients have decreased Nfat1.
Wang says the mice and human studies suggest that Nfat1 may be a key factor for maintaining a healthy metabolic balance in the joint cartilage that covers the ends of bones. As a result, Nfat1 holds promise as a target for predicting, preventing and treating osteoarthritis at the early stage. For example, individuals with blood tests that show decreased levels of Nfat1 could be at risk for osteoarthritis. If further exams confirm the existence of early-stage osteoarthritis, an Nfat1 stimulator could be used to stop the progression of the disease. If osteoarthritis does not yet exist, an Nfat1 stimulator could be used for prevention of Nfat1 deficiency-related osteoarthritis.
Because Nfat1 may suppress the expression of multiple catabolic factors in joint tissues, Nfat1 could be a more effective anti-osteoarthritis target than previously tested drug candidates that only inhibit a single catabolic molecule.
In 2009, Wang filed a patent describing the role of Nfat1 deficiency in osteoarthritis and the various ways the protein could be used against the disease. The United States Patent and Trademark Office granted the patent last fall.
The Nfat1 patent is assigned to the University of Kansas. Wang worked with an office in Lawrence, the Center for Technology and Commercialization, which helps faculty members determine if their ideas need protection through a patent, trademark or copyright.
Wang's research into Nfat1 deficiency and osteoarthritis receives funding from the National Institutes of Health and the U.S. Department of Defense.