Osteoarthritis may begin with subtle stiffening of the bone beneath the joint cartilage, not with the cartilage wearing away. This project tests that hypothesis by measuring, in three dimensions, how strain patterns shift across cartilage and bone in healthy and early-diseased knees. Despite affecting 240 million people worldwide—including 18% of people over 45 in England—the root cause of osteoarthritis remains unknown. Current treatments manage symptoms but do not stop progression. The central gap is whether bone changes precede cartilage damage or vice versa. This work combines high-resolution X-ray CT, mechanical testing, and digital volume correlation on human knee tissue from total replacement surgery and on animal models of both spontaneous and post-traumatic osteoarthritis. If the research confirms that bone stiffening triggers cartilage breakdown, it could shift treatment strategies toward preserving or modifying subchondral bone early in the disease. That might lead to therapies that delay or prevent joint failure, reducing the need for knee replacements and the associated surgical and economic burden. The project is fundamental science—it will not produce a treatment directly—but understanding the sequence of tissue failure is a prerequisite for designing interventions that interrupt the disease at its true origin.
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Osteoarthritis (OA) is one of the most prevalent and disabling chronic degenerative diseases with a 7-fold increase in its incidence predicted by 2030 and is one of the leading global health risks of non-communicable diseases. An estimated 240 million individuals worldwide have symptomatic OA, including 10% of men and 18% of women age 60 and older (World Health Organization. Chronic rheumatic conditions 1. In the England 18.2% of people aged 45 and over have osteoarthritis of the knee whilst 10.9% of people aged 45 and over have osteoarthritis of the hip2. Despite years of research, understanding the aetiology and pathogenesis of OA remains incomplete, and treatments have been largely unsuccessful 3. It has been speculated that the osteoarthritic process may be initiated by an increase in the thickness, volume and stiffness in the subchondral bone4 with the hypothesis that OA induced, either spontaneously or through damage to the joint tissues leads to changes to the subchondral bone resulting in abnormal strain patterns in the articular cartilage. The aim of the project is to measure 3D full-field strain patterns within cartilage, subchondral and trabecular bone in both healthy joints and those with early osteoarthritis (OA) in order to answer the overarching research question: What changes occur at the subchondral bone and articular cartilage interface during the, initiation, progression and pathology of both spontaneous and post traumatic osteoarthritis and how does this affect the strain in the cartilage and other knee joint tissues? The aim of the study will be achieved by combining laboratory-based high-resolution X-ray computed tomography (XCT), in situ mechanical testing and digital volume correlation (DVC), with nano-indentation in specimens from humans and in animal models with spontaneous and post traumatic OA. Human cartilage will be obtained from tibial specimens donated by patients undergoing total knee replacement. Although some regions of the retrieved human knee cartilage will have frank OA other regions may appear to be unaffected though it is unlikely that these areas will have normal cartilage. This hypothesis will be examined through the following objectives: Using DVC and nanoindentation the mechanical behaviour of articular cartilage, calcified cartilage and subchondral-trabecular bone in models of early spontaneous OA and PTOA will be assessed and compared . Histology and immunohistochemistry will be used to measure the pathological changes in the cartilage Using similar methods to those above, the strain patterns and mechanical properties in adjacent knee joint tissues (i.e. menisci, ligaments) in animals with spontaneous OA and PTOA will be measured. Investigating the strain distribution of articular cartilage in areas showing no or little evidence of OA from human tibial plateau, resected during TKR surgery, allowing us to confirm whether OA in the animal models is representative of degeneration in human OA. Understanding of OA development and progression has the potential to be further expanded by exploring other tissue of the joint (i.e. menisci, ligaments) This will have a major impact on the future development of treatment for the disease, reducing this societal and economic burden.
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