Spotlight on Research 2007

December 2007 (historical)

"Smurfs" May Cause Osteoarthritis

If you grew up in the 1980s — or had children who did — you probably know Smurfs as the friendly blue cartoon characters who showed up everywhere from Saturday morning television to lunch boxes and ice shows. But for NIAMS-supported osteoarthritis (OA) researchers, "Smurfs" are neither blue nor necessarily friendly; they're a potentially harmful type of enzyme (full name: Smad Ubiquitination Regulatory Factors), which controls the response of cells to growth factors. Researchers believe a particular form of the enzyme, Smurf2, may hold important clues to the development of OA and quite possibly its prevention.

Smurf2 controls whether a cartilage cell matures and calcifies into hard bone, which is a good thing when it's turned on in areas of the body where we are supposed to have hard bone, says Randy Rosier, M.D., Ph.D., director of the Center of Research Translation in Orthopaedics and senior associate dean for clinical research at the University of Rochester. But when Smurf2 is active in joint cartilage — perhaps as the result of a cartilage injury — it may set off a chain reaction that leads to the steady deterioration of the cartilage that normally comprises the joint surface. When this happens, cartilage breaks down, resulting in damage to the weight-bearing surface of a joint — in other words, OA.

Dr. Rosier believes Smurf2 may be the reason as many as half of people who suffer joint injuries later develop OA in the injured joint. To test his suspicion, he has teamed up with University of Rochester sports medicine surgeon Michael Maloney, M.D., to examine tissue samples from healthy patients without arthritis who have sustained an injury to the meniscus (the crescent-shaped piece of cartilage that cushions the knee joint) to determine the level of Smurf2 in their cartilage at the beginning of the trial.

In addition, the researchers will use magnetic resonance imaging (MRI) to measure the cartilage at the time of injury and again three years later. If MRI results confirm the team's earlier findings, the MRIs of patients with high Smurf2 expression will show the beginning signs of OA as measured by hardening of the cartilage and bone loss.

"Our ultimate goal is to create a simple diagnostic test to determine whether a person with a knee injury has a high level of Smurf2 enzyme in their cartilage," says Dr. Rosier, whose work is being supported by one of a special type of NIAMS grant called a Center of Research Translation (CORT) grant. CORT grants require centers to encompass at least three projects, including one clinical and one basic research study. The grants are awarded to research programs that show promise of quickly translating basic science discoveries into patient treatments.

People found to have high levels of Smurf2 could be advised to stop high-intensity, wear-and-tear activity to slow the onset of arthritis and lessen its intensity, says Dr. Rosier. Eventually, the researchers hope to create an injection that will stop Smurf2's ability to turn on the calcification and degeneration process in cartilage that leads to osteoarthritis.

The study is currently enrolling patients. Anyone interested in participating, should contact study coordinator Kelly Unsworth by e-mail (, phone (585-273-1465) or fax (585-276-2177).

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the 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