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A protein found to increase with age may hold the key to repairing damaged knee cartilage, according to a new study.
Researchers have discovered that blocking the activity of a protein called 15-PGDH can restore cartilage in the knees of aging mice, making it thicker and more functional – resembling healthy, younger cartilage. The treatment also showed promise in preventing the development of osteoarthritis after a knee injury.
The findings, published in Science, suggest a potential new approach to treating osteoarthritis, a common joint condition affecting millions worldwide. Osteoarthritis currently has limited treatment options, often relying on pain management rather than addressing the underlying cartilage damage.
Small Protein Inhibitor, Significant Impact
The research team initially compared cartilage in the knees of young and old mice, finding that older mice had approximately twice as much 15-PGDH in their cartilage. This observation led them to investigate whether the protein played a role in the development and progression of osteoarthritis.
To test this, older mice were given an inhibitor to block the activity of 15-PGDH, first through abdominal injections, and later directly into the knee joint. In both cases, the deteriorating cartilage in the knees showed noticeable thickening and improved function.
Further experiments involved mice with knee injuries. Those treated with the inhibitor twice a week for four weeks were significantly less likely to develop osteoarthritis compared to mice receiving a control treatment. The treated mice also exhibited more natural movement and were able to bear more weight on the injured leg.
Remarkably, the inhibitor also showed positive effects on human cartilage. Researchers tested the treatment on cartilage tissue from patients with osteoarthritis that had been removed during knee replacement surgery. After one week of treatment in the lab, this human cartilage showed reduced levels of 15-PGDH and increased formation of new cartilage.
“We’ve found a new way to regenerate cartilage,” said research leader Helen Blau in a statement. “This could be big medical news for the treatment of osteoarthritis.”
Team member Nidhi Bhutani added, “A large group of existing cells in the cartilage changed their behavior due to the inhibitor, causing the cartilage to begin to heal itself. This is very promising – the degree of healing could be greatly increased.”
A Potential End to Osteoarthritis?
Osteoarthritis is a widespread health concern, affecting approximately one in five adults in the United States. The condition is also a rapidly growing chronic illness in the Netherlands, where an estimated 1.5 million people currently live with osteoarthritis.
Currently, there is no cure for osteoarthritis, and treatment typically focuses on managing pain. “Until now, there has been no drug that directly addresses the cause of cartilage loss,” Bhutani explained. “This inhibitor allows the cartilage to repair itself quickly.”
While the results are encouraging, researchers caution that the study primarily used mice, and further research is needed to determine if the findings will translate to humans. However, the positive response observed in human cartilage samples provides a hopeful sign.
The team has already begun follow-up research using a 15-PGDH inhibitor and initial clinical trials suggest it could be safe and effective for humans. “The first clinical trials show that a 15-PGDH inhibitor could be safe and effective for people,” Blau said. “We hope that more research will follow. Imagine: joint prostheses may not be necessary in the future.”
We’ve covered this topic before, see for example Artrose van Dolly het schaap blijkt alles mee te vallen and ‘Michelangelo leed aan artrose, maar werkte stug door’. Or read this article: We moeten écht meer bewegen: dit zijn de voordelen voor gezond oud worden.
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