Sizable regeneration of damaged or lost cartilage remains impossible in practice, but also a highly desirable goal given the prevalence of osteoarthritis. The best that has been achieved to date in clinical practice results from one specific implementation of stem cell therapy, Cartistem. Other stem cell therapies haven't done as well in this context. You may recall that inhibition of 15-PGDH was shown to improve muscle function in old mice. That work has since moved on to initial clinical trials of a small molecule drug, developed by Epirium Bio. Here, researchers show that the same approach can produce some degree of cartilage regrowth, also in old mice.
Blocking the function of 15-PGDH with a small molecule results in an increase in old animals' muscle mass and endurance. Conversely, expressing 15-PGDH in young mice causes their muscles to shrink and weaken. 15-PGDH has also been implicated in the regeneration of bone, nerve, and blood cells. In each of these tissues, regeneration is due to increases in the proliferation and specialization of tissue-specific stem cells.
Osteoarthritis occurs when a joint is stressed by aging, injury, or obesity. The chondrocytes begin to release pro-inflammatory molecules and to break down collagen, which is the primary structural protein of cartilage. When collagen is lost, the cartilage thins and softens; the accompanying inflammation causes the joint swelling and pain that are hallmarks of the disease. Under normal circumstances, articular cartilage rarely regenerates. Although some populations of putative stem or progenitor cells capable of generating cartilage have been identified in bone, attempts to identify similar populations of cells in the articular cartilage have been unsuccessful.
When researchers compared the amount of 15-PGDH in the knee cartilage in young versus old mice, they saw that, as in other tissues, levels increased about two-fold with age. They next experimented with injecting old animals with a small molecule drug that inhibits 15-PGDH activity - first into the abdomen, which affects the entire body, then directly into the joint. In each case, the knee cartilage, which was markedly thinner and less functional in older animals as compared with younger mice, thickened across the joint surface. Further experiments confirmed that the chondrocytes in the joint were generating hyaline, or articular, cartilage, rather than less-functional fibrocartilage. Similar results were observed in animals with knee injuries.
Link: https://med.stanford.edu/news/all-news/2025/11/joint-cartilage-aging.html
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