The Duke team set out to learn whether the increased body fat of obesity causes an inflammatory response in joints an imbalance of the immune system signaling proteins called cytokines and other chemicals in osteoarthritis.
They studied mice that were leptin-deficient or deficient in leptin receptors mice that didn't have any effective leptin in their bodies. Both types of mice overate and gained weight. Then they compared the study mice with normal mice to document knee osteoarthritis. The measurements included pro- and anti-inflammatory cytokines present in arthritis, and several tests to assess bone changes in the knees of the mice.
The knee bones of the leptin-free, obese mice did change, but without forming osteoarthritis. The levels of inflammatory cytokines, which correlate with arthritis, were largely unchanged in these mice. The results suggested that leptin may have a dual role in the development of osteoarthritis by regulating both the skeletal and immune systems.
What does this mean for people? "Obesity is still the number one preventable risk factor of osteoarthritis, but now it seems body fat by itself is not what is causing it," Guilak said. "If you are obese, there are benefits to losing weight in terms of arthritis. For example, if you are obese and lose just 10 pounds, pain decreases significantly. Pain modulation is another clue it might be a chemical or systemic metabolic effect, rather than just a mechanical effect of less weight on the joints."
As with many studies that yield unanticipated findings, "we have a lot of additional questions and experiments that need to be done to further understand how leptin mediates the development of osteoarthritis," Griffin said.
"With obesity and osteoarthritis, t
|Contact: Mary Jane Gore|
Duke University Medical Center