Osteoarthritis, a degenerative joint disease affecting one in five adults in the United States and impacting as many as one in two individuals over the age of 60, may soon have a new treatment option. Researchers at Stanford Medicine have demonstrated the ability to reverse cartilage degradation in aging joints, and even prevent arthritis following injury, in preclinical studies. The findings, published in late January , offer a potential pathway toward regenerative therapies that could ultimately reduce the need for joint replacement surgery.
Currently, treatment for osteoarthritis primarily focuses on pain management and, in severe cases, surgical joint replacement – procedures that can be challenging for patients and involve lengthy recovery periods. The Stanford research, however, targets the underlying cause of cartilage loss, offering a potentially disease-modifying approach. The study centers around a protein called 15-PGDH, identified as a “gerozyme” – a protein whose prevalence increases with age and drives tissue dysfunction.
In experiments with aging mice, injections blocking the activity of 15-PGDH reversed naturally occurring cartilage loss in the knee joints. The treatment prevented the development of arthritis after injuries mimicking anterior cruciate ligament (ACL) tears, common among athletes and active individuals. Remarkably, human cartilage samples obtained from knee replacement surgeries also responded positively to the treatment, exhibiting signs of new cartilage formation in laboratory settings.
“In our country, osteoarthritis affects two out of every three people over the age of 60,” explains Prof. Dr. Kadriye Öneş, Head of the Department of Physical Medicine and Rehabilitation at Health Sciences University Hamidiye Faculty of Medicine. “It frequently affects the knee joint, but can also occur in other joints. The research conducted on animals showed that injections of a gerozyme inhibitor, administered twice weekly for four weeks, significantly reduced the likelihood of developing osteoarthritis in mice. Specifically, the reduction in both age-related osteoarthritis and osteoarthritis developing after an anterior cruciate ligament injury demonstrates the treatment’s potential for both protective and restorative effects.”
The potential of this research extends beyond simply alleviating symptoms. Prof. Dr. İsmail Demirkale, an Orthopedics and Traumatology Specialist at Liv Hospital Vadi İstanbul, emphasizes the significance of the findings. “The study showed that aged mice with thinned knee cartilage experienced cartilage thickening, osteoarthritis development after ACL injury was reduced, existing cartilage cells reverted to a younger genetic profile, and human cartilage tissue obtained from knee replacement surgeries showed signs of regeneration in the lab. These results are scientifically very exciting. The fact that adult cartilage cells can be reprogrammed without the use of stem cells is an important development.”
However, Prof. Dr. Demirkale cautions against premature optimism. “Claims circulating on social media that osteoarthritis surgeries will become obsolete are not scientifically accurate. The dose, safety, long-term data, and potential side effects must be tested in clinical phase studies. If this mechanism works safely and effectively in humans, it could potentially be a treatment that changes the course of the disease. This could represent a paradigm shift in osteoarthritis treatment. But we are still at the beginning of the road.”
The research also holds promise for preventative strategies. Prof. Dr. Gökhan Polat, from the Department of Orthopedics and Traumatology at Istanbul Faculty of Medicine, explains that researchers identified an increase in 15-PGDH protein in cartilage tissue as aging progresses and developed a drug to block this protein. “The researchers have begun phase 1 studies on muscle weakness with this molecule and hope to begin studies on cartilage soon. Osteoarthritis, which is characterized by the breakdown of aging joint cartilage, develops multifactorially in patients. The studies were initially conducted on mice, an animal with a high ability to self-renew. However, the positive results obtained are still promising and will open the door to future phase 1 volunteer human studies.”
The approach differs from current regenerative techniques, such as stem cell or PRP (platelet-rich plasma) therapies, which have shown limited success in consistently generating new cartilage. Prof. Dr. Mehmet Ağırman, a Physical Therapy and Rehabilitation Specialist at Medipol Mega, notes that the Stanford research demonstrated increased production of new and functional cartilage at the cellular level. “After the study on mice, the researchers saw that human cartilage tissue also tended to grow again in the laboratory environment. With the same treatment, an increase was observed in the production of new and functional cartilage at the cellular level. This has begun to give hope that this approach may be effective not only in animal models but also in humans. If the clinical studies are successful in the coming years, drugs that rebuild cartilage may also be included among our treatment options for osteoarthritis, in addition to pain relievers and prosthetic surgeries.”
While the research is still in its early stages, the findings represent a significant step forward in the search for effective osteoarthritis treatments. An oral version of the 15-PGDH inhibitor is already undergoing clinical trials for age-related muscle weakness, suggesting a potential pathway for broader application of this therapeutic approach. Further research and clinical trials will be crucial to determine the safety and efficacy of this treatment in humans, but the initial results offer a beacon of hope for the millions affected by this debilitating condition.
