A Stanford Medicine-led team has found that suppressing a protein called 15-PGDH can regrow damaged knee cartilage in mice and trigger repair in human cartilage samples. The protein, which the researchers call a gerozyme because it accumulates with age, normally breaks down prostaglandin E2. Blocking it with a small molecule shifted existing cartilage cells — chondrocytes — into a more youthful gene-expression state, allowing them to rebuild the joint surface. The results were published in Science.
In old mice, the treatment reversed naturally occurring cartilage loss. In a separate group, mice given the inhibitor after knee injuries similar to human ACL tears did not develop osteoarthritis. The most direct human evidence came from cartilage discarded during knee replacement surgeries: after exposure to the same inhibitor, those samples began producing new, functional joint cartilage. The authors note this is the first drug intervention to show such dramatic regeneration, and they believe it could eventually be delivered as an oral medicine or injection.
Osteoarthritis affects roughly one in five U.S. adults and costs about $65 billion annually in direct care. Current treatments only manage symptoms, and severe cases often end in joint replacement. This study suggests that damaged cartilage is more repairable than assumed, but the work is still in preclinical stages. The researchers caution that human trials are needed before the approach can be used clinically.