RT Journal Article
SR Electronic
T1 The Effects of Monosodium Urate Monohydrate Crystals on Chondrocyte Viability and Function: Implications for Development of Cartilage Damage in Gout
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 2067
OP 2074
DO 10.3899/jrheum.130708
VO 40
IS 12
A1 Ashika Chhana
A1 Karen E. Callon
A1 Bregina Pool
A1 Dorit Naot
A1 Gregory D. Gamble
A1 Michael Dray
A1 Rocco Pitto
A1 Jarome Bentley
A1 Fiona M. McQueen
A1 Jillian Cornish
A1 Nicola Dalbeth
YR 2013
UL http://www.jrheum.org/content/40/12/2067.abstract
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.