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10-12-2015 | Microbiome | Review | Article

Does lipopolysaccharide-mediated inflammation have a role in OA?

Authors: Zeyu Huang, Virginia Byers Kraus

Abstract

The nature of the gastrointestinal microbiome determines the reservoir of lipopolysaccharide, which can migrate from the gut into the circulation, where it contributes to low-grade inflammation. Osteoarthritis (OA) is a low-grade inflammatory condition, and the elevation of levels of lipopolysaccharide in association with obesity and metabolic syndrome could contribute to OA. A 'two- hit' model of OA susceptibility and potentiation suggests that lipopolysaccharide primes the proinflammatory innate immune response via Toll-like receptor 4 and that progression to a full-blown inflammatory response and structural damage of the joint results from coexisting complementary mechanisms, such as inflammasome activation or assembly by damage-associated molecular patterns in the form of fragmented cartilage-matrix molecules. Lipopolysaccharide could be considered a major hidden risk factor that provides a unifying mechanism to explain the association between obesity, metabolic syndrome and OA.

Subject terms: Inflammation • Microbiota • Obesity• Osteoarthritis

Nat Rev Rheumatol 2016;12:123–129. doi:10.1038/nrrheum.2015.158

Osteoarthritis (OA), the most common form of joint disease and a major cause of pain and disability, affects ≥320 million individuals globally, on the basis of age-standardized prevalence-rate estimates1. For economic and ethical reasons, identification of the optimal treatment for individual patients is a pressing concern that is particularly challenging, owing to the heterogeneity of OA and the very large number of those affected. The goal of pairing patients with the most appropriate therapies will be achieved, in part, by the identification and characterization of subsets of disease.

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