Cartilage Regrowth Could Transform Arthritis Treatment, Stanford Research Suggests - Video

Blocking an ageing-related protein helped restore damaged knee cartilage in older mice and reduced osteoarthritis after knee injuries, according to a study published in Science.

Researchers focused on 15-PGDH, a protein that becomes more abundant with age and breaks down prostaglandin E2, involved in tissue repair. In older mice, 15-PGDH levels were about twice those in younger animals.

The researchers used an inhibitor to block 15-PGDH. Treatment given systemically or directly into the knee increased cartilage thickness in aged mice. The newly formed tissue was hyaline articular cartilage, which allows joints to move smoothly.

The treatment also protected mice after injuries designed to mimic ACL injury. Mice received the inhibitor twice weekly for four weeks and were much less likely to develop osteoarthritis. Treated animals also showed better movement and greater weight-bearing on the injured leg.

Experiments suggested that treatment did not activate stem cells. Instead, existing cartilage cells called chondrocytes changed their gene activity and adopted a younger state. Genes linked to cartilage degradation and inflammation became less active, while genes involved in healthy cartilage formation and extracellular matrix maintenance increased.

Researchers also tested cartilage samples collected during knee replacement surgery. After one week of treatment, human cartilage showed fewer cells expressing 15-PGDH and reduced activity of genes associated with cartilage breakdown and fibrocartilage formation. The samples also began producing articular cartilage.

However, these findings remain preclinical. Its ability to regenerate cartilage or prevent osteoarthritis in humans has not been established. Although an oral 15-PGDH inhibitor has entered early clinical testing for muscle weakness, clinical trials are needed to determine whether the approach is safe and effective for arthritis.

If confirmed in humans, the strategy could offer a disease-modifying treatment for osteoarthritis and reduce the need for joint replacement.

REFERENCES: Mamta Singla, et al.; Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration. Science, 2026; 391 (6789): 1053 DOI: 10.1126/science.adx6649