Fig. 2 ∣. Osteoarthritis risk factors and synovitis.

Among the risk factors associated with osteoarthritis (OA) development and progression, trauma, mechanical loading, comorbidities and diet–microbiome interactions are also related to synovitis. Injury to the meniscus or ligaments and intra-articular fractures lead to the development of synovitis. Aberrant and excessive loading is a known risk factor for developing OA, and subseguent shear stress and compression induce production of inflammatory mediators such as nitric oxide synthase (NOS), IL-6 and IL-8, which contribute to OA pathogenesis. Synovitis has also been related to obesity and type 2 diabetes mellitus. Dietary habit, which has been demonstrated to increase pain prevalence in patients with OA, is one of the factors that influence the composition of the gut microbiome. Microbial dysbiosis (that is, alteration in gut microbiome composition) favours inflammation and metabolic syndrome, as well as changes in intestinal permeability and metabolic endotoxaemia, which correlates with recruitment of activated pro-inflammatory synovial macrophages. LPS, lipopolysaccharide.