Provoking Greater Stem Cell Activity to Reverse Cartilage Loss in Osteoarthritis

Osteoarthritis is a degenerative joint disease characterized by loss of cartilage and associated bone tissue. It is a major, widespread issue in old age. A promising study in mice here suggests that osteoarthritis might be reversed via suitable manipulation of stem cell and progenitor cell populations capable of producing cartilage regrowth. In this model, the known contributing factors, such as chronic inflammation in and around joint tissues, are contributing factors because they suppress the activity of the small population of cells responsible for maintenance of cartilage.

Osteoarthritis is the degeneration of cartilage and other tissues in joints and is the most common form of arthritis in Australia, with one in five people over the age of 45 having the condition. Often described as a 'wear and tear' condition, factors such as ageing, obesity, injury, and family history contribute to the progression of osteoarthritis. Researchers have discovered a novel population of stem cells - marked by the Gremlin 1 protein - responsible for the progression of osteoarthritis. Treatment with fibroblast growth factor 18 (FGF18) stimulated the proliferation of Gremlin 1 cells in joint cartilage in mice, leading to significant recovery of cartilage thickness and reduced osteoarthritis.

Gremlin 1 cells present opportunities for cartilage regeneration and their discovery will have relevance to other forms of cartilage injury and disease, which are notoriously challenging to repair and treat. It challenges the categorisation of osteoarthritis as wear and tear. "With this new information, we are now able to explore pharmaceutical options to directly target the stem cell population that is responsible for the development of articular cartilage and progression of osteoarthritis."

Though this discovery is limited to animal models, there are genetic similarities to human samples, and human trials are ongoing. Results of a five-year clinical trial study using FGF18, known clinically as Sprifermin, were published in 2021 with potential long-term clinical benefit and no safety concerns. Phase 3 of the Sprifermin trial is ongoing, and researchers envision public access to this treatment soon.

Link: https://www.eurekalert.org/news-releases/1006425