Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation
- 18 January 2011
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (5), 2088-2093
- https://doi.org/10.1073/pnas.1012743108
Abstract
Uric acid (UA) is known to activate the NLRP3 (Nacht, leucine-rich repeat and pyrin domain containing protein 3) inflammasome. When activated, the NLRP3 (also known as NALP3) inflammasome leads to the production of IL-18 and IL-1β. In this cohort of subjects with knee osteoarthritis (OA), synovial fluid uric acid was strongly correlated with synovial fluid IL-18 and IL-1β. Synovial fluid uric acid and IL-18 were strongly and positively associated with OA severity as measured by both radiograph and bone scintigraphy, and synovial fluid IL-1β was associated with OA severity but only by radiograph. Furthermore, synovial fluid IL-18 was associated with a 3-y change in OA severity, on the basis of the radiograph. We conclude that synovial fluid uric acid is a marker of knee OA severity. The correlation of synovial fluid uric acid with the two cytokines (IL-18 and IL-1β) known to be produced by uric acid-activated inflammasomes and the association of synovial fluid IL-18 with OA progression, lend strong support to the potential involvement of the innate immune system in OA pathology and OA progression.This publication has 65 references indexed in Scilit:
- Caught red-handed: uric acid is an agent of inflammationJCI Insight, 2010
- Uric acid promotes an acute inflammatory response to sterile cell death in miceJCI Insight, 2010
- Autophagy is a protective mechanism in normal cartilage, and its aging‐related loss is linked with cell death and osteoarthritisArthritis & Rheumatism, 2010
- A Role of IgM Antibodies in Monosodium Urate Crystal Formation and Associated AdjuvanticityThe Journal of Immunology, 2009
- Association of bone scintigraphic abnormalities with knee malalignment and painAnnals Of The Rheumatic Diseases, 2008
- Are joints affected by gout also affected by osteoarthritis?Annals Of The Rheumatic Diseases, 2007
- Molecular identification of a danger signal that alerts the immune system to dying cellsNature, 2003
- Action of biologically-relevant oxidizing species upon uric acid. Identification of uric acid oxidation productsChemico-Biological Interactions, 1990
- Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.Proceedings of the National Academy of Sciences of the United States of America, 1981
- Radiological Assessment of Osteo-ArthrosisAnnals Of The Rheumatic Diseases, 1957