Investigating the properties of synovial fluid extracellular vesicles from patients with knee osteoarthritis and with or without obesity

Abstract

There is increasing evidence that osteoarthritis (OA) is caused by an active process of inflammation and degeneration, rather than a passive age-related process of wear and tear as previously thought. Obesity (BMI ≥ 30) not only increases the overall risk of developing knee OA by approximately two-fold, but also increases the severity of disease. New Zealand has the third highest rates for obesity in the Organisation for Economic Cooperation and Development (OECD) countries, and as a result there is an increased incidence of OA in NZ associated with the increased BMI. Obesity-associated OA has been recognized as a subtype of OA having specific disease pathology and risk factors, and obesity impacts OA beyond its weight-bearing implications, as obese individuals show a higher prevalence of OA even in nonweight-bearing joints like the wrist and hand. It can also lead to chronic systemic inflammation but how this translates to the joints, and the molecular mechanisms underlying the association between the obesity related soluble factors and the metabolic complications that have been implicated in OA pathogenesis have not been studied or understood fully to date. For instance, the means by which different tissues within the joint communicate with each other, such as extracellular vesicles, may have significant effects on the disease progression, encouraging the study of the OA joint in its totality. Extracellular Vesicles (EVs) carry proinflammatory molecules in their cargo which can alter during development of OA and might be influenced by obesity-associated systemic inflammation. EVs are found in synovial fluid (SF), articular cartilage and in the supernatants of synovial cells and chondrocytes. As inflammatory changes in joint tissues may be mediated by EVs present in the SF, SF EVs in arthritic joints could contribute to anomalous gene expression and alterations in the extracellular matrix of the articular cartilage. Thus, the characteristics and the molecular contents within EVs might be involved in the increased inflammatory signalling seen within the joints of the OA patients with obesity. The research outlined in this study aims to understand the differences in the OA subtypes by characterising biochemical and proteomic contents of SF EVs from patients with knee OA, with or without obesity to understand their role in the development of knee OA in people with obesity.