Published on: Nov 27, 2025
A Stanford Medicine–led study has found that an injection blocking a protein associated with aging can reverse naturally occurring cartilage loss in the knee joints of older mice. The treatment also prevented arthritis after knee injuries similar to ACL tears that commonly occur in athletes and active individuals. An oral version of this therapy is already in clinical trials for age-related muscle weakness.
Human knee tissue samples — including the extracellular matrix and cartilage-producing chondrocytes — also responded to the treatment by generating new, functional cartilage.
These findings indicate that cartilage lost due to aging or arthritis may one day be restored using either an oral medication or a localized injection, potentially reducing the need for future knee or hip replacement surgeries.
The therapy targets the underlying cause of osteoarthritis — a degenerative joint disease affecting one in five adults in the U.S. and costing more than $65 billion each year. Currently, no available drug can slow or reverse osteoarthritis; most treatments focus on pain management or joint replacement.
The protein 15-PGDH, known as a gerozyme because its activity increases with age, is a key regulator of aging processes. First identified in 2023 by the same research group, gerzymes contribute to age-related tissue decline. Blocking 15-PGDH with a small molecule has been shown to increase muscle mass and endurance in older mice, whereas boosting the protein in young mice leads to muscle weakening. It also plays a role in the regeneration of bone, nerve, and blood cells.
In many tissues, regeneration occurs through stem cells. However, in cartilage, chondrocytes regain a more youthful gene expression profile without stem cell involvement.
This is a completely new way of regenerating adult tissue and holds significant promise for treating arthritis caused by aging or injury, said Helen Blau, PhD. We initially expected stem cells to be involved, but clearly they are not. It’s incredibly exciting.
Dramatic regeneration
Millions of people experience joint pain and swelling as they age, said Bhutani. This is a major unmet need. Until now, no drug has directly targeted the cause of cartilage loss. But this gerozyme inhibitor triggers a dramatic regeneration of cartilage unlike anything previously reported.
The human body contains three main types of cartilage: elastic, fibrocartilage, and hyaline. Hyaline (articular) cartilage — the smooth, friction-reducing tissue in joints — is the type most commonly damaged in osteoarthritis. When joints experience aging, injury, or obesity, chondrocytes release inflammatory molecules and begin degrading collagen, resulting in thinning cartilage, swelling, and pain. Under normal conditions, articular cartilage has very limited capacity to regenerate, and efforts to locate stem cells within it have largely been unsuccessful.
Earlier studies from Blau’s lab showed that prostaglandin E2, essential for muscle stem cell function, is broken down by 15-PGDH. Inhibiting 15-PGDH raises prostaglandin E2 levels and boosts tissue regeneration in young mice.
Suspecting a similar mechanism in cartilage, the team examined aging joints and found that 15-PGDH levels doubled in knee cartilage with age. Treating older mice with a 15-PGDH inhibitor — either systemically or through direct joint injection — significantly increased cartilage thickness, restoring it to a more youthful state. Tests confirmed that chondrocytes were producing healthy hyaline cartilage, not the less effective fibrocartilage.
The extent of cartilage regeneration in aged mice was truly surprising, Bhutani said. The improvement was remarkable.
Source: https://med.stanford.edu/news/all-news/2025/11/joint-cartilage-aging.html
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