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Does lipopolysaccharide-mediated inflammation have a role in OA?

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.

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Figure 1: The complement and TLR pathways in organ pathology.
Figure 2: Pathophysiological mechanisms underlying regulation of systemic lipopolysaccharide concentrations.
Figure 3: Two-hit model of OA pathogenesis involving lipopolysaccharide.

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Acknowledgements

Z.H. wishes to acknowledge funding support by the China Health Ministry Program (201302007). V.B.K. wishes to acknowledge funding support by NIH/NIA OAIC P30-AG-028716.

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Correspondence to Virginia Byers Kraus.

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Huang, Z., Kraus, V. Does lipopolysaccharide-mediated inflammation have a role in OA?. Nat Rev Rheumatol 12, 123–129 (2016). https://doi.org/10.1038/nrrheum.2015.158

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