A Stanford Medicine-led study says an experimental treatment targeting an age-related protein restored knee cartilage in older mice and reduced arthritis after severe joint injury. The findings, published in Science, also showed early effects in human cartilage samples from knee replacement surgeries, but the approach has not yet been tested for cartilage repair in patients.
The treatment blocks 15-PGDH, a protein researchers describe as a “gerozyme,” meaning it becomes more active with age and may contribute to declining tissue function. Previous work by the same group linked 15-PGDH to age-related muscle loss and tissue regeneration in mice. An oral version of a 15-PGDH inhibitor is already in clinical trials for muscle weakness.
Osteoarthritis affects about one in five U.S. adults and causes joint pain, stiffness and swelling. Current care generally focuses on pain management, physical therapy and, in advanced cases, joint replacement. No approved drug reverses cartilage loss.
In the mouse experiments, 15-PGDH levels were higher in older cartilage. When aged mice received the inhibitor, either by body-wide injection or directly into the knee, researchers observed thicker cartilage across the joint surface. Tests indicated the new tissue was hyaline cartilage, the smooth joint cartilage damaged in osteoarthritis, rather than scar-like fibrocartilage.
The treatment also appeared protective after injuries designed to mimic ACL tears. Treated mice were less likely to develop osteoarthritis, walked more normally and placed more weight on the injured limb than untreated mice.
Cell analyses suggested the drug did not work by activating stem cells. Instead, existing cartilage-producing cells, called chondrocytes, shifted toward gene activity associated with healthier, younger cartilage. Human osteoarthritis samples exposed to the inhibitor for one week showed similar changes and began forming new articular cartilage.
Researchers said clinical trials will be needed; several authors reported patents or company ties involving the technology and licensing.