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Monosodium urate monohydrate crystals inhibit osteoblast viability and function: implications for development of bone erosion in gout
  1. Ashika Chhana1,
  2. Karen E Callon1,
  3. Bregina Pool1,
  4. Dorit Naot1,
  5. Maureen Watson1,
  6. Greg D Gamble1,
  7. Fiona M McQueen2,
  8. Jillian Cornish1,
  9. Nicola Dalbeth1
  1. 1Bone Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand
  2. 2Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand
  1. Correspondence to Dr Nicola Dalbeth, Bone Research Group, Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, New Zealand; n.dalbeth{at}auckland.ac.nz

Abstract

Background Bone erosion is a common manifestation of chronic tophaceous gout.

Objectives 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.

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Footnotes

  • Funding This study was funded by a University of Auckland Doctoral Scholarship (AC) and the Auckland Medical Research Foundation.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the New Zealand Ministry of Health Northern Regional Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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