Osteoarthritis affects about one in five adults and is driven by the gradual breakdown of articular (hyaline) cartilage, the smooth tissue that allows joints to move without friction. Once damaged, this cartilage has very limited ability to heal, leaving pain management or joint replacement as the main treatment options. No approved drug currently targets the root cause of cartilage loss.
The new approach focuses on an enzyme called 15-PGDH, known as a “gerozyme” because its levels rise with age and contribute to tissue decline. Researchers found that this enzyme roughly doubles in aging knee cartilage. When older mice were given a small-molecule inhibitor that blocks 15-PGDH—either systemically or directly into the knee—their thinning cartilage thickened and regained healthy structure.
The treatment also worked in mice with knee injuries similar to ACL tears, which often lead to osteoarthritis in humans. Treated animals were far less likely to develop arthritis and showed improved movement compared to untreated mice.
Importantly, the team tested human cartilage samples taken from knee replacement surgeries. After one week of treatment, the tissue showed reduced cartilage-degrading activity and early signs of new, functional cartilage formation.
Unlike many regenerative therapies, this process did not rely on stem cells. Instead, existing cartilage cells were reprogrammed into a more youthful, repair-focused state.
With oral versions of the drug already in early clinical trials for muscle aging, researchers hope similar trials for cartilage regeneration could follow—raising the possibility of treating arthritis without surgery in the future.
REFERENCE: Mamta Singla, Yu Xin Wang, Elena Monti, Yudhishtar Bedi, Pranay Agarwal, Shiqi Su, Sara Ancel, Maiko Hermsmeier, Nitya Devisetti, Akshay Pandey, Mohsen Afshar Bakooshli, Adelaida R. Palla, Stuart Goodman, Helen M Blau, Nidhi Bhutani. Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration. Science, 2025; DOI: 10.1126/science.adx6649
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