Knee cartilage: A Stanford Medicine-led team has reported that blocking an age-linked enzyme helped worn knee cartilage regrow in older mice and reduced the likelihood of arthritis developing after knee injuries, offering a potential new approach for osteoarthritis that aims to repair tissue rather than only manage pain.
In the study, published in Science, researchers targeted 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a protein that rises with age and breaks down prostaglandin E2 (PGE2), a molecule involved in tissue repair. The team found that 15-PGDH levels were higher in the articular cartilage of aged or injured mice, and that inhibiting the enzyme with a small-molecule drug promoted regeneration of articular cartilage and reduced osteoarthritis-associated pain in animal models.
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Beyond age-related wear, the researchers tested the inhibitor in mice with knee injuries resembling ACL tears. According to Stanford Medicine, a series of injections given twice a week for four weeks after injury markedly lowered the chance that osteoarthritis developed in the joint, and treated animals showed more normal movement and weight-bearing compared with controls.
The work also included experiments on human cartilage. Tissue collected during knee replacement surgeries responded to the inhibitor in laboratory conditions, showing reduced expression of genes linked to cartilage breakdown and the formation of less-functional fibrocartilage, while beginning to regenerate articular cartilage.
A notable finding was the proposed mechanism: instead of relying on stem cells, existing cartilage cells (chondrocytes) appeared to shift their gene activity toward a more youthful pattern after treatment, with cell subtypes associated with degradation decreasing and those linked to healthy articular cartilage increasing.
Osteoarthritis is among the most common joint disorders and a major cause of disability. In the United States, an estimated 32.5 million adults live with osteoarthritis, and direct medical costs have been estimated at about $65 billion annually.
However, there is currently no approved drug widely recognised as able to halt or reverse the underlying cartilage loss, leaving symptom control and joint replacement as the main options for advanced disease.
An oral 15-PGDH inhibitor is already being developed for age-related muscle weakness, with the company developing the drug reporting positive Phase 1 safety and activity signals in healthy volunteers.
The Stanford team said they hope a similar clinical study will be launched to test whether the approach can safely support cartilage regeneration in people.
