Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation.

نویسندگان

  • Anna E Denoble
  • Kim M Huffman
  • Thomas V Stabler
  • Susan J Kelly
  • Michael S Hershfield
  • Gary E McDaniel
  • R Edward Coleman
  • Virginia B Kraus
چکیده

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.

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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 108 5  شماره 

صفحات  -

تاریخ انتشار 2011