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

被引：211

作者：

Denoble, Anna E. ^{[1
]}

Huffman, Kim M. ^{[1
]}

Stabler, Thomas V. ^{[1
]}

Kelly, Susan J. ^{[1
]}

Hershfield, Michael S. ^{[1
]}

McDaniel, Gary E. ^{[1
]}

Coleman, R. Edward ^{[2
]}

Kraus, Virginia B. ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 05期

基金：

美国国家卫生研究院;

关键词：

arthritis; inflammation; interleukin-18; interleukin-1; beta; tumor necrosis factor alpha; CRYSTAL DEPOSITION DISEASE; SYNOVIAL-FLUID COMPONENTS; MONOSODIUM URATE CRYSTALS; NECROSIS-FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; KNEE OSTEOARTHRITIS; INTERLEUKIN-1; IL-1; CELL-DEATH; CARTILAGE; IDENTIFICATION;

D O I：

10.1073/pnas.1012743108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-1 beta. In this cohort of subjects with knee osteoarthritis (OA), synovial fluid uric acid was strongly correlated with synovial fluid IL-18 and IL-1 beta. 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-1 beta 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-1 beta) 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.

引用

页码：2088 / 2093

页数：6

共 64 条

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