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New Insights into Common Knee Injuries

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Duke Health News 919-660-1306

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.

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