A team of researchers at Stanford Medicine has reported a breakthrough that could reshape the future treatment of osteoarthritis, a degenerative joint disease affecting millions worldwide. In a study published in Science, scientists found that blocking a protein linked to ageing restored cartilage in older mice and prevented arthritis from developing after knee injuries. Early laboratory tests on human cartilage samples also showed signs of regeneration.


Injectable drug restored joint cartilage in aged and injured mice

While the findings remain in the experimental stage, researchers say the results suggest that future therapies could potentially reduce or delay the need for joint replacement surgery.

In a statement released by Stanford Medicine, Helen Blau, PhD, professor of microbiology and immunology, said, “This is a new way of regenerating adult tissue, and it has significant clinical promise for treating arthritis due to ageing or injury. We were looking for stem cells, but they are clearly not involved. It’s very exciting.”

Blau, who leads the Baxter Laboratory for Stem Cell Biology and holds the Donald E. and Delia B. Baxter Foundation Professorship, and Nidhi Bhutani, PhD, associate professor of orthopaedic surgery, are the study’s senior authors.

Osteoarthritis affects roughly one in five adults in the United States and generates tens of billions of dollars annually in direct healthcare costs. The possibility of a drug capable of restoring cartilage represents a major shift from current symptom-based treatment approaches.

Targeting a Protein Linked to Ageing

The study focused on a protein known as 15-PGDH, described by researchers as a gerozyme, or an enzyme associated with ageing-related tissue decline. Levels of 15-PGDH increase as the body ages. The protein breaks down prostaglandin E2, a molecule involved in tissue repair and regeneration.

“Interestingly, prostaglandin E2 has been implicated in inflammation and pain,” Blau said in the statement. “But this research shows that, at normal biological levels, small increases in prostaglandin E2 can promote regeneration.”

Previous research by the same team found that blocking 15-PGDH improved muscle strength in older mice. In the latest study, scientists investigated whether the same approach could influence cartilage health. Cartilage, particularly the smooth hyaline cartilage that lines joints, has a very limited ability to regenerate once damaged. Osteoarthritis develops when cartilage deteriorates due to age, injury, or mechanical stress, leading to inflammation, swelling, and chronic pain. Currently, treatments focus on managing symptoms or surgically replacing damaged joints. No approved drugs can reverse cartilage loss.

In the new experiments, older mice were injected with a small-molecule inhibitor of 15-PGDH. Some animals received systemic injections, while others were treated directly in the knee joint. In both cases, researchers observed thickening of cartilage that had previously become thin and degraded with age. Additional testing confirmed that the regenerated tissue resembled functional hyaline cartilage rather than fibrocartilage, which is mechanically weaker.

“Cartilage regeneration to such an extent in aged mice took us by surprise,” Nidhi Bhutani said in the Stanford statement. “The effect was remarkable.”

Preventing Arthritis After Injury

The researchers also tested the drug in mice with knee injuries resembling anterior cruciate ligament (ACL) tears, a common sports injury that significantly increases the long-term risk of osteoarthritis. Mice treated twice weekly with the inhibitor for four weeks after injury were far less likely to develop osteoarthritis than untreated animals. Treated mice also demonstrated improved movement and weight-bearing ability in the injured limb.

Interestingly, the treatment appeared to reprogram existing cartilage cells, known as chondrocytes, rather than relying on stem cells. Analysis showed a shift in gene expression toward a more youthful cartilage profile, including reduced expression of inflammatory markers and cartilage-degrading genes.

“The mechanism is quite striking and really shifted our perspective about how tissue regeneration can occur,” Bhutani said in the statement. “It’s clear that a large pool of already existing cells in cartilage is changing their gene expression patterns.”

Early Signals in Human Tissue

To explore potential relevance for people, the Stanford researchers treated cartilage samples obtained from patients undergoing knee replacement surgery for osteoarthritis. After one week of exposure to the 15-PGDH inhibitor, the tissue showed fewer cells producing the ageing-associated enzyme and early molecular signs consistent with cartilage regeneration.

An oral 15-PGDH inhibitor has already completed Phase 1 safety testing for age-related muscle weakness, demonstrating safety and biologic activity in healthy volunteers. Researchers hope similar trials will eventually evaluate its effects on joint cartilage. Blau added, “Phase 1 clinical trials of a 15-PGDH inhibitor for muscle weakness have shown that it is safe and active in healthy volunteers. Our hope is that a similar trial will be launched soon to test its effect in cartilage regeneration. We are very excited about this potential breakthrough. Imagine regrowing existing cartilage and avoiding joint replacement.”

However, experts caution that results in mice do not always translate to humans. Many regenerative therapies have shown promise in animal models but faced challenges in clinical development. Independent clinical trials will be necessary to determine whether the approach is safe and effective in patients with osteoarthritis. For now, the findings represent an early but potentially significant step in understanding how ageing-related cartilage loss might one day be reversed.