A study led by Stanford Medicine researchers has found that an injection blocking a protein linked to aging can reverse the natural loss of knee cartilage in older mice. The same treatment also stopped arthritis from developing after knee injuries that resemble ACL tears, which are common among athletes and recreational exercisers. Researchers note that an oral version of the treatment is already being tested in clinical trials aimed at treating age-related muscle weakness.
Human cartilage samples taken from knee replacement surgeries also responded positively. These samples included both the supportive extracellular matrix of the joint and cartilage-producing chondrocyte cells. When treated, the tissue began forming new, functional cartilage.
Together, the findings suggest that cartilage lost due to aging or arthritis may one day be restored using either a pill or a targeted injection. If successful in people, such treatments could reduce or even eliminate the need for knee and hip replacement surgery.
A Direct Attack on Osteoarthritis
Osteoarthritis is a degenerative joint disease that affects about one in five adults in the United States and generates an estimated $65 billion each year in direct health care costs. Current treatments focus on managing pain or replacing damaged joints surgically. There are no approved drugs that can slow or reverse the underlying cartilage damage.
The new approach targets the root cause of the disease rather than its symptoms, offering a potential shift in how osteoarthritis is treated.
The Role of a Master Aging Enzyme
The protein at the center of the study is called 15-PGDH. Researchers refer to it as a gerozyme because its levels increase as the body ages. Gerozymes were identified by the same research team in 2023 and are known to drive the gradual loss of tissue function.
In mice, higher levels of 15-PGDH are linked to declining muscle strength with age. Blocking the enzyme using a small molecule boosted muscle mass and endurance in older animals. In contrast, forcing young mice to produce more 15-PGDH caused their muscles to shrink and weaken. The protein has also been connected to regeneration in bone, nerve, and blood cells.
In most of these tissues, repair happens through the activation and specialization of stem cells. Cartilage appears to be different. In this case, chondrocytes change how their genes behave, shifting into a more youthful state without relying on stem cells.
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