"Super-Healing” Mice Helping to Understand Post-Traumatic Arthritis

A new strain of laboratory mice that resists inflammation following a knee injury and avoids developing arthritis in the long term could aid the development of new therapies for treating posttraumatic Arthritis.

Researchers from Duke University (Durham, NC, USA) examined the differences in inflammatory response between two types of mice; one type known as "superhealers” (MRL/MpJ) versus a strain of control mice (C57BL/6), by examining cytokine--signaling molecules produced by cells in response to injury that promote inflammation and an increase in temperature--levels. The control mice showed a greater than 700-fold increase in the expression of interleukin 1β (IL-1β) in the first four hours after a fracture, and 37-fold difference at seven days after the fracture.

The "superhealer” mice showed a similar trend, but in much lower amounts: a 70-fold peak in expression at day zero down to a 3.5-fold increase by day seven. A second cytokine, tumor-necrosis factor α (TNF-α), was also expressed at a significantly higher rate in the control mice after the fracture (from a 13-fold peak just after fracture to five-fold at seven days), while the superhealer mice showed no change in their levels of TNF-α at all over time. The researchers also studied the mice's synovial (joint) fluid and blood serum to measure actual levels of the cytokines; overall, the control mice again showed significantly higher serum levels and synovial fluid levels of cytokines compared with the superhealers. The study was presented at the Orthopedic Research Society meeting, held during February 2009 in Las Vegas (NV, USA).

"The superhealer can almost regenerate tissue,” said lead author Bridgette Furman, Ph.D., a research analyst at Duke. "We thought, ‘if they can regenerate cartilage in the ear, what about cartilage in the knee?' This happened in our pilot study, and we now have taken these results further and learned what happens in terms of inflammation. If you can figure out why the animal is a superhealer and apply that to people, then you may help prevent the development of arthritis.”

In future studies the researchers plan to use rheumatoid arthritis drugs such as anakinra (an IL-1 receptor antagonist) and etanercept (a TNF blocker) in normal mice immediately after a fracture to find out if by inhibiting the inflammatory cytokines long-term arthritis could be prevented.

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