Reactive nitrogen and oxygen species in interleukin-1-mediated DNA damage associated with osteoarthritis

C. M. Davies, F. Guilak, J. B. Weinberg, B. Fermor

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Objective: Osteoarthritis (OA) is associated with increased levels of reactive nitrogen and oxygen species and pro-inflammatory cytokines, such as interleukin-1 (IL-1). Nitric oxide (NO) can mediate a number of the catabolic effects of IL-1 in articular cartilage. The aims of this study were to determine if OA cartilage shows evidence of DNA damage, and if IL-1 could induce DNA damage in non-OA cartilage by increasing NO or superoxide. Methods: Articular chondrocytes were isolated from porcine femoral condyles and embedded in 1.2% alginate. The effects of 24 h incubation with IL-1, the nitric oxide synthase 2 (NOS2)-selective inhibitor, the free radical scavenger superoxide dismutase (SOD), the NO donor NOC18, or the combined NO and peroxynitrite donor SIN-1 on DNA damage were tested, using the "comet" assay. NO production was measured using the Griess assay. The type of oxidative damage present was assessed using a modified comet assay. Results: OA cartilage had significantly more DNA damage than non-OA cartilage (P < 0.001). IL-1 caused an increase in DNA damage (P < 0.01), which was associated with increased NO production (P < 0.01). Both oxidative DNA strand breaks and base modifications of purines and pyrimidines were observed. IL-1-induced DNA damage was inhibited by an NOS2 inhibitor or by SOD (P < 0.01). Furthermore, NOC18 or SIN-1 caused DNA damage (P < 0.001). Conclusion: Our work shows chondrocytes in osteoarthritic cartilage exhibit DNA damage, and that IL-1 induces DNA damage and reactive oxygen and nitrogen species in non-OA chondrocytes in alginate.

Original languageEnglish
Pages (from-to)624-630
Number of pages7
JournalOsteoarthritis and Cartilage
Volume16
Issue number5
DOIs
StatePublished - May 1 2008
Externally publishedYes

Keywords

  • Articular cartilage
  • Interleukin-1
  • Osteoarthritis
  • Reactive oxygen species

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