Gene protecting against osteoarthritis identified: study


By Xu Jing

CHICAGO, Dec. 2 (Xinhua) -- Working in a mouse model of osteoarthritis, one of the most common problems associated with aging, researchers at Washington University School of Medicine in St. Louis have found that a molecule, FoxO1, seems to be involved in the development of osteoarthritis and may be a useful treatment target.

The researchers found that when the mice in the experiments had elevated levels of the FoxO1 molecule, that was previously linked to diabetes, cancer and muscle atrophy, osteoarthritis's progress was slowed or even reversed. They believe the molecule interferes with cartilage damage and the development of arthritis by enhancing a process called autophagy in the arthritic joint.

In these experiments, the researchers found that autophagy was disrupted in the mice with reduced levels of FoxO1 and that the process was enhanced in animals with higher levels of the molecule.

"In other words, maintaining a higher level of autophagy seemed to be beneficial to maintaining these cartilage cells and, thus, maintaining a healthy knee joint," said co-corresponding author Jie Shen, an assistant professor of orthopedic surgery.

This raises the possibility of delivering FoxO1 to arthritic joints through nanotechnology as a way to regulate autophagy and keep joints healthier, said senior investigator Regis J. O'Keefe, a professor of orthopaedic surgery.

"In mice with injuries that typically progress to become osteoarthritis, the knee joints still appear normal about a week after injury," O'Keefe explained. "But when we measure autophagy in the cartilage after injury to those same knee joints, although the joints themselves look fine, the autophagy process already is shut off. The injury completely turns it off, and once autophagy is off, the cartilage begins to degenerate."

He said if FoxO1 can alter that process in people, protecting cartilage from damage as it does in mice, it eventually may be possible to prevent or delay millions of future knee and hip replacement surgeries.

Osteoarthritis is one of the most common problems associated with aging, and although there are therapies to treat the pain that results from the breakdown of the cartilage that cushions joints, there are no available therapies to modify the course of the disease. The disease affects more than 32 million people in the United States alone.

The study, posted on the university's website on Tuesday, has been published online in Proceedings of the National Academy of Sciences.

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