Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation
AE Denoble, KM Huffman, TV Stabler… - Proceedings of the …, 2011 - National Acad Sciences
AE Denoble, KM Huffman, TV Stabler, SJ Kelly, MS Hershfield, GE McDaniel, RE Coleman…
Proceedings of the National Academy of Sciences, 2011•National Acad SciencesUric 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 …
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 …
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.
National Acad Sciences