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Research has found that osteoarthritis (OA) is not a collection of separate diseases, as many scientists have previously speculated, but rather a single condition with a common core underlying biological pathways.

The STEpUP OA (Synovial fluid to detect Endotypes by Unbiased Proteomics in OA) project, , is the largest and most comprehensive molecular analysis of osteoarthritis tissue to date. The findings provide a long-awaited answer to a fundamental question that has challenged the OA field for decades and opens the door to more targeted and effective treatments for millions of people living with OA.

The study brought together scientists from Europe, Canada, and the UK, and includes several industry and charity partners. Researchers analysed synovial fluid – the lubricating fluid in the knee joint – from more than 1,300 people with established knee OA, using a cutting-edge proteomics platform (SomaScan v4.1, SomaLogic) that measured over 7,000 proteins per sample.

By comparing molecular patterns in these samples, the team sought to answer a crucial question: is OA really “one disease,” or are there multiple distinct subtypes (endotypes), each requiring its own treatment approach?

Dr Fiona Watt, Clinical Associate Professor in Rheumatology helped to design and drive the consortium work during her time at University of Oxford, supported by her UKRI Future Leaders Fellowship, and continues as part of its leadership after her move to 51³Ô¹ÏÍø. The research was led by the Kennedy Institute of Rheumatology at the University of Oxford.

Dr Watt said: “This work represents the culmination of 8 years of collaboration across several international universities and industry. At its heart was answering one of the fundamental questions of osteoarthritis, providing evidence from large scale data to better understand whether there were truly discrete subgroups that might explain the differences we see in this enigmatic disease. We hope that this new knowledge from this window into the osteoarthritic knee joint will pave the way to better methods for predicting disease worsening  – in work ongoing in the consortium - and to support the development of new treatments for osteoarthritis in the future.”

Linking samples to factors of osteoarthritis

Linked to each sample were details about the participant, such as age, biological sex, body mass index, i.e. known risk factors in osteoarthritis. By examining these characteristics, the study showed that while OA has a single molecular fingerprint, there is biological variation that is influenced by factors like obesity, sex, and age. 

In participants with obesity, for example, the team observed additional inflammatory signals. Not immune cell driven inflammation seen in conditions like rheumatoid arthritis, but a tissue-injury response likely linked to mechanical stress. Such differences may explain why some patients progress faster or respond differently to therapies, and they could help researchers design more targeted clinical trials.

The findings may help reshape the search for effective treatments for OA, which remains one of the leading causes of disability worldwide and has no approved disease-modifying therapies.

“This work provides a clear map of the molecular landscape of OA and offers a valuable resource for researchers and pharmaceutical companies,” said Dr Thomas Perry, Senior post-doctoral Molecular Epidemiologist at the KIR and first author of the study. ‘It will allow us to match patients to therapies much more precisely - a crucial step towards developing long-awaited treatments that slow or halt disease progression."

The STEpUP OA dataset, which is available to the research community, is expected to drive a new wave of discovery. Scientists can use it to explore key biological pathways, identify which patients are most likely to benefit from a given treatment, and design better-targeted clinical trials, potentially reducing costs and increasing the chances of success.

For patients, the study provides reassurance that OA is a single disease with well-defined biological pathways, rather than a mixture of disease subtypes each with different biology. It also reinforces the importance of lifestyle factors such as weight management, since obesity is shown to amplify inflammatory signals within the joint.

Professor Lucy Donaldson, Director of Research at Arthritis UK said: "Understanding the biology of osteoarthritis will help us develop better, more personalised treatments for people with osteoarthritis. People experience OA differently- we know for example, that peri menopausal women face higher risk, and that some people see their symptoms progress far more quickly than others. Understanding the mechanisms of OA is a crucial step towards understanding why the condition varies so much between individuals."

This article has been adapted by a story written by the  

The study was funded by the Kennedy Trust for Rheumatology Research, Arthritis UK and UKRI  and supported by industry partners including Galapagos, Biosplice, Novartis, Fidia, UCB, Nordic Bioscience, Pfizer, GSK and Somalogic.