UNMC Header

Potential disease-modifying drug for osteoarthritis identified

Image with caption: From left, Anna Spagnoli, M.D., and Tieshi Li, Ph.D.

From left, Anna Spagnoli, M.D., and Tieshi Li, Ph.D.

Researchers have gained a better understanding of how osteoarthritis (OA) occurs and have identified a potential new drug that could be used to treat OA, a debilitating disease expected to affect 67 million people in the United States by 2030.

The research is detailed in the May 8 issue of "Science Translational Medicine."

The collaborative research project involved scientists at four U.S. institutions -- UNMC, Rush University Medical Center, University of North Carolina at Chapel Hill and Duke University -- as well as Tongji Medical College in China and Gulhane Military Medical School in Turkey.

The lead author on the study is Tieshi Li, Ph.D., assistant professor, pediatrics, at UNMC. The senior author on the study is Anna Spagnoli, M.D., chair of the UNMC Department of Pediatrics and director of the Child Health Research Institute, pediatrician-in-chief and senior vice president for Children's Hospital & Medical Center.

Dr. Spagnoli joined UNMC and Children's earlier this year after working previously at Rush University Medical Center and the University of North Carolina at Chapel Hill. Dr. Li worked with Dr. Spagnoli at Rush University Medical Center and joined her team in Omaha.

Using several animal models and human samples from people with osteoarthritic joints, the researchers determined that the TGF-beta type II signaling receptor (TGFBR2) regulates joint development during fetal life as well as joint maintenance through the lifespan. It does this by modulating key components of a family of inflammatory cytokines called the IL-36 system.

Researchers discovered that if subjects lacked TGFBR2 that it led to OA and impaired movements. In aging mice that naturally develop OA and in mice with post-traumatic OA, researchers found a profound decrease in TGFBR2.

In human joints, the study found that the decrease in TGFBR2 correlated with the severity of the OA. They also found that the decrease in TGFBR2 was associated with an increase of IL-36-alpha and a decrease in its antagonist (IL-36 receptor antagonist) in humans and all four animal models studied.

These findings indicated that TGFBR2 is a potential target for treating OA. Researchers then focused on the IL-36 system as a novel and critical downstream mediator of TGFBR2 and a potential target to treat OA.

With most of the experiments performed by Dr. Li, the IL-36 receptor antagonist was injected in knee joints affected by OA -- and in the key finding of the study -- it was found that the injection improved the OA in mice and in human cartilage cells from people with OA and decreased metalloproteinases, enzymes that destroy joint cartilage.

"This is truly a significant breakthrough," Dr. Spagnoli said. "Currently, we are lacking any drugs that are capable of preventing, treating or halting the progression of OA, and the ultimate treatment is surgical joint replacement. Further studies need to be done, but we are excited by the positive response seen with the injection of the IL-36 receptor antagonist. It should provide hope to OA sufferers."

Osteoarthritis facts

  • Osteoarthritis (OA) is sometimes called degenerative joint disease or "wear and tear" arthritis. It is the most common chronic condition of the joints.
  • It occurs when the cartilage or cushion between joints breaks down leading to pain, stiffness and swelling. The most common symptoms of OA are stiffness - particularly first thing in the morning or after resting - and pain. Affected joints may get swollen after extended activity.
  • Symptomatic knee OA occurs in 10% of men and 13% of women aged 60 years or older.
  • OA has no specific cause. Several factors lead to the development of OA, including excess weight, injury, overuse and genetics. People who have family members with OA are more likely to develop OA. People who have hand OA are more likely to develop knee OA.
  • The risk of developing OA increases with age. Most people over age 60 have osteoarthritis to some degree, but its severity varies. Even people in their 20s and 30s can get osteoarthritis. In people over age 50, more women than men have osteoarthritis.
  • OA treatment options include weight management, physical activity, medications, joint replacement surgery and a variety of other techniques.
  • Two of every three adults in the U.S. have some form of arthritis.
  • OA is the single most common cause of disability in adults in the world.
  • It's estimated that OA affects 31 million Americans, and the number is growing rapidly because of the aging of the population.
  • By 2040, it's anticipated that more than 78 million people in the U.S. will be affected by OA.
  • Some Asian populations have lower risk for OA.

UNMC Wordmark