Background Gout is the most prevalent inflammatory arthropathy in young men, in which clinical manifestations are triggered by the deposits of monosodium urate (MSU) crystals in and around joints. From a clinical perspective, gouty attacks and tophaceous deposits have been associated to nodal osteoarthritis [1,2].
Objectives To determine the molecular mechanisms associating MSU crystal deposits with chondrocyte activation and changes in articular cartilage.
Methods Primary cultures of synoviocytes were activated with MSU crystals for 24 h, the resulting supernatant was used as a supplementary conditioning basal medium (CBM) for 24 h chondrocyte growth. The expression level profile of cytokines (IL-6, IL-8) and nerve growth factor (NGF) in the supernatant was measured. Production of reactive oxygen and nitrogen species, such as O2●, H2O2, and NO●, was also measured intracellularly.
Results Upon activation by MSU crystals, synoviocytes increased secretion of IL-6 and IL-8, as well as intracellular production of O2●, H2O2, and NO● in comparison to non-stimulated synoviocytes. Additionally, the chondrocytes incubated with CBM for 24 h increased significantly IL-6, IL-8, and NGF levels, as well as O2●, H2O2, and NO● levels when compared to non-stimulated chondrocytes. Secretion of these soluble mediators was even higher than the one observed in the synoviocytes and chondrocytes directly stimulated with MSU crystals.
Conclusions Pro-inflammatory cytokine secretion induced by MSU crystals in synoviocytes triggers chondrocyte activation, intensifying the articular inflammatory state in gouty attacks. Furthermore, the increase in reactive species (particularly NO●, which inhibits proteoglycan synthesis) compromises the homeostasis of the extracellular matrix of the cartilage. Finally, overproduction of NGF and H2O2 by the chondrocyte functions a pain modulator during gout attacks.
Fam AG, et al. Gouty arthritis in nodal osteoarthritis. J Rheumatol 1996; 23:684–9.
Roddy E, et al. Gout and nodal osteoarthritis: a case-control study. Rheumatology (Oxford) 2008; 47:732–3.
Disclosure of Interest None declared
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