title: The effects of monosodium urate monohydrate crystals on chondrocyte viability and function: implications for development of cartilage damage in gout.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the Bone and Joint Research Group, Department of Medicine and the Department of Orthopaedic Surgery, University of Auckland, Auckland; and the Department of Histology, Waikato Hospital, Hamilton, New Zealand.
authors.forename: Ashika
authors.initials: A
authors.lastname: Chhana
authors.forename: Karen E
authors.initials: KE
authors.lastname: Callon
authors.forename: Bregina
authors.initials: B
authors.lastname: Pool
authors.forename: Dorit
authors.initials: D
authors.lastname: Naot
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Gamble
authors.forename: Michael
authors.initials: M
authors.lastname: Dray
authors.forename: Rocco
authors.initials: R
authors.lastname: Pitto
authors.forename: Jarome
authors.initials: J
authors.lastname: Bentley
authors.forename: Fiona M
authors.initials: FM
authors.lastname: McQueen
authors.forename: Jillian
authors.initials: J
authors.lastname: Cornish
authors.forename: Nicola
authors.initials: N
authors.lastname: Dalbeth
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D002356:Cartilage / Q000187:drug effects* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects*; D019902:Chondrocytes / Q000187:drug effects* / Q000473:pathology; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006073:Gout / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D009924:Organ Culture Techniques; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000378:metabolism; D014527:Uric Acid / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D014527:Uric Acid
keywords: CARTILAGE; CHONDROCYTE; GOUT; URATE CRYSTALS