Different types of fibroblasts are organized in different layers in the joint and are responsible for two very different forms of arthritis: osteoarthritis and rheumatoid arthritis, new research suggests.
Targeted therapies could alter the behavior of fibroblasts to reduce inflammation and tissue destruction in osteoarthritis and rheumatoid arthritis without the need for long-term immunosuppression or joint replacements, suggest scientists from the Universities of Oxford and Birmingham, in research published in Nature.
“We have identified two different types of fibroblasts in the joint, which, just like the different types of soil, lead to different types of arthritis. The top soil is what goes wrong in osteoarthritis, whereas in rheumatoid arthritis it’s the subsoil that is at fault,” says chief investigator and professor Chris Buckley, in a media release from University of Birmingham.
“We have now discovered a new way to classify, and therefore treat, arthritis based on the underlying cell, rather than just the clinical features and genes involved.
“Current therapies work like weed killer — they kill the weeds but the weeds come back if you don’t continue to apply the weed killer. Our research will facilitate research aimed at changing the top soil, subsoil — or both — to treat arthritis,” continues Buckley, from the University of Birmingham’s Institute of Inflammation and Ageing and Director of Clinical Research at the Kennedy Institute at the University of Oxford.
Minimally invasive biopsies and single-cell sequencing allowed the research team to investigate fibroblast cells and their location in the joint, helping them to ultimately identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or cartilage/bone damage in arthritis, the release notes.
“Rheumatoid arthritis is challenging to treat. It causes chronic inflammation in joints, leading to pain, swelling and, over time, damage to the joint. This is due to the body’s own immune system attacking the joints, which leads to an influx of immune cells in the lining of the joint,” adds first author Dr Adam Croft, currently NIHR Academic Clinical Lecturer in Rheumatology at the University of Birmingham.
“Thanks to advances in technology we have now, we have been able to identify which fibroblasts are pathogenic in arthritis and how they contribute to disease.
Importantly, we found that by getting rid of these fibroblasts from the joint we could reduce the influx of immune cells to the joint, leading to less inflammation and destruction.
“These findings mean we now have a clear rationale for developing drugs that can target joint fibroblasts directly and provide more effective treatment for persistent disease,” Croft concludes, in the release.
[Source(s): University of Birmingham, Science Daily]
