PT  - JOURNAL ARTICLE
AU  - Ashika Chhana
AU  - Karen E. Callon
AU  - Bregina Pool
AU  - Dorit Naot
AU  - Gregory D. Gamble
AU  - Michael Dray
AU  - Rocco Pitto
AU  - Jarome Bentley
AU  - Fiona M. McQueen
AU  - Jillian Cornish
AU  - Nicola Dalbeth
TI  - The Effects of Monosodium Urate Monohydrate Crystals on Chondrocyte Viability and Function: Implications for Development of Cartilage Damage in Gout
AID  - 10.3899/jrheum.130708
DP  - 2013 Dec 01
TA  - The Journal of Rheumatology
PG  - 2067--2074
VI  - 40
IP  - 12
4099  - http://www.jrheum.org/content/40/12/2067.short
4100  - http://www.jrheum.org/content/40/12/2067.full
SO  - J Rheumatol2013 Dec 01; 40
AB  - Objective. Cartilage damage is frequently observed in advanced destructive gout. The aim of our study was to investigate the effects of monosodium urate monohydrate (MSU) crystals on chondrocyte viability and function. Methods. The alamarBlue assay and flow cytometry were used to assess the viability of primary human chondrocytes and cartilage explants following culture with MSU crystals. The number of dead chondrocytes in cartilage explants cultured with MSU crystals was quantified. Real-time PCR was used to determine changes in the relative mRNA expression levels of chondrocytic genes. The histological appearance of cartilage in joints affected by gout was also examined. Results. MSU crystals rapidly reduced primary human chondrocyte and cartilage explant viability in a dose-dependent manner (p < 0.01 for both). Cartilage explants cultured with MSU crystals had a greater percentage of dead chondrocytes at the articular surface compared to untreated cartilage (p = 0.004). Relative mRNA expression of type II collagen and the cartilage matrix proteins aggrecan and versican was decreased in chondrocytes following culture with MSU crystals (p < 0.05 for all). However, expression of the degradative enzymes ADAMTS4 and ADAMTS5 was increased (p < 0.05 for both). In joints affected by gout, normal cartilage architecture was lost, with empty chondrocyte lacunae observed. Conclusion. MSU crystals have profound inhibitory effects on chondrocyte viability and function. Interactions between MSU crystals and chondrocytes may contribute to cartilage damage in gout through reduction of chondrocyte viability and promotion of a catabolic state.