Abstract
ObjectivesEpidemiological and experimental studies have established obesity to be an important risk factor for osteoarthritis (OA), however, the mechanisms underlying this link remains largely unknown. Here, we studied local inflammatory responses in metabolic-OA.MethodsWistar rats were fed with control diet (CD) and high-carbohydrate, high-fat diet (HCHF) for period of 8 and 16 weeks. After euthanasia, the knees were examined to assess the articular cartilage changes and inflammation in synovial membrane. Further IHC was conducted to determine the macrophage-polarization status of the synovium. In addition, CD and HCHF synovial fluid was co-cultured with bone marrow-derived macrophages to assess the effect of synovial fluid inflammation on macrophage polarisation.ResultsOur study showed that, obesity induced by a high-carbohydrate, high-fat (HCHF) diet is associated with spontaneous and local inflammation of the synovial membranes in rats even before the cartilage degradation. This was followed by increased synovitis and increased macrophage infiltration into the synovium and a predominant elevation of pro-inflammatory M1 macrophages. In addition, bone marrow derived macrophages, cultured with synovial fluid collected from the knees of obese rats exhibited a pro-inflammatory M1 macrophage phenotype.ConclusionOur study demonstrate a strong association between obesity and a dynamic immune response locally within synovial tissues. Furthermore, we have also identified synovial resident macrophages to play a vital role in the inflammation caused by the HCHF diet. Therefore, future therapeutic strategies targeted at the synovial macrophage phenotype may be the key to break the link between obesity and OA.
Highlights
Accumulating epidemiological and experimental evidence supports an association between obesity and a higher incidence of osteoarthritis (OA) [1,2,3]
Obesity induced by a high-carbohydrate, high-fat (HCHF) diet is associated with spontaneous and local inflammation of the synovial membranes in rats even before the cartilage degradation
We have previously reported that rats fed a HCHF diet develop symptoms characteristic of metabolic syndrome and cardiovascular changes, in particular central obesity, elevated blood pressure, impaired glucose tolerance, insulin resistance, non-alcoholic fatty liver disease and dyslipidaemia; this is a relevant model of diet-induced metabolic syndrome in humans [28, 29]
Summary
Accumulating epidemiological and experimental evidence supports an association between obesity and a higher incidence of osteoarthritis (OA) [1,2,3]. High sucrose (HFS) DIO rat model, after a 12-week post-obesity induction, DIO rats demonstrated increased OA-like cartilage changes, and systemic and local synovial fluid inflammatory markers and accumulation of adiposity [13]. Additional study found that obesity and dietary fatty acid content regulate the development of OA [16]. These studies together provide strong evidence that obesity is strongly linked with OA development
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