title: Monosodium urate monohydrate crystals inhibit osteoblast viability and function: implications for development of bone erosion in gout.
abstract: BACKGROUND
  Bone erosion is a common manifestation of chronic tophaceous gout.
  
  
  OBJECTIVE
  To investigate the effects of monosodium urate monohydrate (MSU) crystals on osteoblast viability and function.
  
  
  METHODS
  The MTT assay and flow cytometry were used to assess osteoblast cell viability in the MC3T3-E1 and ST2 osteoblast-like cell lines, and primary rat and primary human osteoblasts cultured with MSU crystals. Quantitative real-time PCR and von Kossa stained mineralised bone formation assays were used to assess the effects of MSU crystals on osteoblast differentiation using MC3T3-E1 cells. The numbers of osteoblasts and bone lining cells were quantified in bone samples from patients with gout.
  
  
  RESULTS
  MSU crystals rapidly reduced viability in all cell types in a dose-dependent manner. The inhibitory effect on cell viability was independent of crystal phagocytosis and was not influenced by differing crystal length or addition of serum. Long-term culture of MC3T3-E1 cells with MSU crystals showed a reduction in mineralisation and decreased mRNA expression of genes related to osteoblast differentiation such as Runx2, Sp7 (osterix), Ibsp (bone sialoprotein), and Bglap (osteocalcin). Fewer osteoblast and lining cells were present on bone directly adjacent to gouty tophus than bone unaffected by tophus in patients with gout.
  
  
  CONCLUSIONS
  MSU crystals have profound inhibitory effects on osteoblast viability and differentiation. These data suggest that bone erosion in gout occurs at the tophus-bone interface through alteration of physiological bone turnover, with both excessive osteoclast formation, and reduced osteoblast differentiation from mesenchymal stem cells.
authors.affiliation: Bone Research Group, Department of Medicine, University of Auckland, Auckland, 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: Maureen
authors.initials: M
authors.lastname: Watson
authors.forename: Greg D
authors.initials: GD
authors.lastname: Gamble
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: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001862:Bone Resorption / Q000209:etiology / Q000473:pathology*; D001842:Bone and Bones / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D006073:Gout / Q000150:complications / Q000473:pathology*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects* / Q000502:physiology; D010010:Osteoclasts / Q000473:pathology; D051381:Rats; D014527:Uric Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014527:Uric Acid