Osteoarthritis may be treatable and reversible, new study shows

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Current osteoarthritis treatments manage the symptoms without addressing the underlying disease, but a new study from the University of Adelaide suggests the condition is treatable and reversible.

Osteoarthritis is the degeneration of cartilage and other joint tissues and is the most common form of arthritis in Australia, with one in five people over the age of 45 having the condition.

It is a long-term and progressive condition that affects people’s mobility and has historically had no cure. It cost the Australian health system an estimated $3.9 billion to treat in 2019-20.

Often described as a ‘wear and tear’ condition, factors such as aging, obesity, trauma and family history contribute to the progression of osteoarthritis.

Researchers at the University of Adelaide have discovered a novel population of stem cells – marked by the Gremlin 1 gene – responsible for the progression of osteoarthritis.

Treatment with fibroblast growth factor 18 (FGF18) stimulates proliferation of Gremlin 1 cells in rat joint cartilage, leading to significant restoration of cartilage thickness and reduction of osteoarthritis.

Gremlin 1 cells present opportunities for cartilage regeneration, and their discovery will be relevant to other types of cartilage injuries and diseases, which are notoriously challenging to repair and treat.

This challenges the classification of osteoarthritis as wear and tear.

“The results of our study reframe osteoarthritis not as a ‘wear and tear’ condition but as an active, and pharmaceutically critical, articular cartilage stem cell loss,” said Dr Jia Ng of the University of Adelaide’s Adelaide Medical School, who co-led the study.

“With this new information, we are now able to explore pharmaceutical options to directly target the stem cell population that is responsible for the progression of articular cartilage and osteoarthritis.”

Although Dr. Ng describes current treatments for osteoarthritis as a “Band-Aid approach,” this new understanding could lead to a pharmaceutical treatment that reverses osteoarthritis and helps address health outcomes associated with the disease.

Known comorbidities of osteoarthritis include heart, pulmonary, and kidney disease, psychiatric and behavioral conditions, diabetes, and cancer.

Our research suggests that there may be new ways to treat the disease rather than just the symptoms, leading to better health outcomes and quality of life for people with osteoarthritis.”

Dr Jia Ng from Adelaide Medical School

Although this discovery is limited to animal models, Dr. Ng said, there are genetic similarities to human samples and human trials are underway.

“We look forward to the results of these trials and contributing to a better understanding of a pharmaceutical mechanism for the treatment of osteoarthritis,” he said.

The results of a five-year clinical trial study using FGF18, known clinically as sprifermin, were published in 2021 with no potential long-term clinical benefit and no safety concerns.

Phase 3 trials of spirformin are underway, and researchers are considering public access to the treatment soon.


Journal Reference:

Ng, J.Q., etc. (2023). Loss of Grem1-derived chondrogenic progenitor cells causes osteoarthritis. Nature communication. doi.org/10.1038/s41467-023-42199-1.

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