Stanford Study Finds New Way to Restore Knee Cartilage

A Stanford Medicine-led team targeted 15-PGDH, an enzyme that becomes more plentiful with age and contributes to declining tissue function. In mouse knee cartilage, its level was about twice as high in older animals as in younger ones. Researchers used a small-molecule inhibitor, either through an abdominal injection that acted throughout the body or by placing it directly into the knee. Older mice had started with cartilage that was thinner and worked less effectively, but treatment increased its thickness across the joint surface.

The rebuilt material was hyaline cartilage—the smooth tissue that helps joint bones glide—not the tougher fibrocartilage. The repair did not come from stem cells. Instead, existing cartilage cells, known as chondrocytes, altered their gene activity and moved toward a younger state. After knee injuries resembling human ACL tears, mice received the drug two times each week over a four-week period. Their risk of developing osteoarthritis fell sharply. This is notable because around half of people with such injuries develop osteoarthritis in that joint within about 15 years.

Human tissue also responded. Cartilage obtained during knee replacement operations started creating functional new joint cartilage after exposure to the inhibitor. Osteoarthritis affects approximately one-fifth of U.S. adults and generates an estimated $65 billion in direct annual medical spending. Available care largely manages symptoms, while severe disease can leave joint replacement as the remaining option. No medicine currently slows or reverses the condition reliably. If the strategy succeeds in people, researchers say it might become a pill or injection that restores cartilage and lowers the need for knee or hip replacements.