New research suggests that the appetite-regulating hormone leptin may play a role in the long-recognized connection between obesity and osteoarthritis (OA). The most common form of arthritis, osteoarthritis is characterized by the breakdown and loss of cartilage and the formation of bony overgrowths in the joints.
Scientists have long known that obesity is the number one preventable risk factor for osteoarthritis, but only in recent years have they ramped up research to understand how obesity and OA are connected.
Traditionally, the connection was assumed to be related to wear and tear. More weight meant a greater load for the joints to bear. But the wear-and-tear theory did not explain why joints in the hand, which do not bear weight, are also affected by OA. To better understand the systemic role obesity might play, Farshid Guilak, Ph.D., director of orthopaedic research in the Department of Surgery at Duke University, and his colleagues studied obese mice.
In their new study, supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and published in the journal Arthritis & Rheumatism, the group studied mice genetically engineered to lack either leptin or leptin receptors on the cells.
Leptin acts in the brain to control appetite, but to do so it must bind to receptors on cells. Removing either the molecule or the receptor has virtually the same effect — no functioning leptin. And for the mice studied, the result of no functioning leptin was a body weight approximately four times that of normal mice — which would seem like the ideal model for studying obesity-related OA. But, the mice didn't develop OA at all. In fact, their joint cartilage was just as healthy, if not more so, than that of normal mice.
Researchers say if they can better understand the molecular mechanisms involved in OA, they may be better able to interfere with them and perhaps prevent the disease or stop its progression.
The Arthritis Foundation also provided funding for this study.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov
Griffin TM, Huebner JL, Kraus VB, Guilak F. Extreme Obesity Due to Impaired Leptin Signaling in Mice Does Not Cause Knee Osteoarthritis. Arthritis & Rheumatism. 2009 Oct;60(10):2935-44.