DURHAM, N.C. – The sort of swelling that occurs when a joint is damaged by injury or degeneration is normally essential to the healing process, but when it comes to the knee, that inflammation can actually interfere with healing.
These findings in experiments with pigs may lead to treatments for injuries or osteoarthritis in the knee, according to Duke University Medical Center orthopedic researchers. There are drugs that can block the action of these immune system proteins that trigger joint inflammation.
The Duke researchers report in the September issue of the journal Arthritis & Rheumatism that two immune system proteins, interleukin-1 (IL-1) and tumor necrosis factor (TNF), block the healing of the damaged pig meniscus, an important layer of buffering tissue within the joint. When agents that counteract the effects of these two proteins were administered directly to the damaged meniscus, the repair process resumed.
The primary function of the meniscus – a type of cartilage located within the knee joint between the thigh bone (femur) and the lower leg bone (tibia) -- is to act as a shock absorber and a distributor of weight within the joint. Nearly 15 percent of all athletic injuries to the knee involve the meniscus, and the breakdown and loss of this tissue ultimately leads to osteoarthritis, the so-called “wear-and-tear” form of the disease.
The researchers, led by Duke postdoctoral fellow Amy McNulty, Ph.D., said there is a need for a new approach to treat these injuries. The most common meniscus injury is a tear. If the tear is small and occurs on the outside of the meniscus, it can be repaired surgically. However, these repairs don’t often work well. If the tear is large, surgeons often have no choice but to remove the torn portion, and sometimes the entire meniscus, which leads to painful movement and ultimately osteoarthritis.
Duke researchers exposed pig knees to various concentrations of IL-1 and TNF. They found that as they increased the amounts of the proteins, the meniscus tissue was less able to repair itself. The range of concentrations of IL-1 and TNF used in the experiment match those found in the joint fluid of humans with rheumatoid arthritis and osteoarthritis, providing further evidence that these proteins could play a role in the disease process.
According to Farshid Guilak, Ph.D., senior member of the research team and director of orthopedic research at Duke, these findings should theoretically help physicians repair knee joints damaged by injury or osteoarthritis.
“There already is a drug that blocks the effects of TNF that is used widely and effectively in patients with rheumatoid arthritis, the form of the disease caused by body’s own immune system attacking the joint,” Guilak said. “Another drug also exists that blocks IL-1 that is being used for rheumatoid arthritis and is currently undergoing clinical trials for osteoarthritis.”
These drugs are administered to the entire body. However, the key to the possible new approach would be to deliver these agents directly into the site of meniscus damage, Guilak said.
The research was funded by the V.A. Research Service, the National Institutes of Health and the Arthritis Foundation, which is sponsoring McNulty’s research. Duke’s Frank Moutos and J. Brice Weinberg were also members of the team.
Journal
Arthritis & Rheumatism