Researchers at Stanford University have discovered a method to restore cartilage in aging knee joints in mice by inhibiting a protein that increases with age. This approach not only reversed cartilage loss in older mice but also prevented the development of arthritis following knee injuries similar to ACL tears in humans. The study's findings also indicated potential for human cartilage tissue, as samples collected during knee replacement surgeries began producing new cartilage when treated with the same method.
The research, led by Stanford Medicine, focused on a protein known as 15-PGDH, which the researchers termed a 'gerozyme' due to its increased abundance with age and its role in tissue degradation. Previous studies indicated that blocking 15-PGDH can enhance muscle mass and endurance in older mice. The current study revealed that, unlike other tissues that rely on stem cells for healing, cartilage cells, or chondrocytes, can revert to a more youthful state by altering their gene activity.
Helen Blau, PhD, a professor of microbiology and immunology, stated, "This is a new way of regenerating adult tissue, and it has significant clinical promise for treating arthritis due to aging or injury." The study, published in the journal Science, included contributions from several researchers, including Nidhi Bhutani, PhD, and Mamta Singla, PhD.
Osteoarthritis, a degenerative joint disease affecting about one in five adults in the U.S., results in painful and swollen joints due to cartilage breakdown. Current treatments primarily manage symptoms rather than address the underlying cause. The Stanford study suggests that targeting 15-PGDH could lead to new treatments that regenerate cartilage and reduce the need for joint replacement surgeries.
In experiments, older mice treated with a small molecule drug to inhibit 15-PGDH showed significant cartilage regeneration, with treated mice exhibiting thicker cartilage and improved joint function compared to untreated mice. The study also explored the effects of the treatment on knee injuries, finding that it significantly reduced the likelihood of developing osteoarthritis post-injury.
The researchers noted that the treatment prompted changes in gene expression among chondrocytes, enhancing the production of hyaline cartilage, which is essential for healthy joint movement. The findings also extended to human cartilage samples, which showed decreased levels of 15-PGDH and signs of cartilage regeneration after treatment.
While the results are promising, the researchers emphasized that clinical trials are necessary to confirm the safety and efficacy of this approach in humans. An oral 15-PGDH inhibitor is already undergoing clinical testing for muscle weakness, with hopes for similar trials aimed at cartilage regeneration in the future. The study received funding from various organizations, including the National Institutes of Health and the Baxter Foundation for Stem Cell Biology.