Influence of oxygen tension on interleukin 1-induced peroxynitrite formation and matrix turnover in articular cartilage

Julie M. Cernanec, J. Brice Weinberg, Ines Batinic-Haberle, Farshid Guilak, Beverley Fermor

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Objective. Osteoarthritis is characterized by the degradation of articular cartilage. The catabolic activity of chondrocytes is partly regulated by nitric oxide (NO), which with superoxide (O2-) leads to the formation of peroxynitrite (OONC-), a potentially damaging reactive species. Cartilage is avascular and functions at reduced oxygen tension. We investigated whether oxygen tension influences the effects of interleukin 1 (IL-1) on peroxynitrite formation and cartilage matrix metabolism. Methods. Porcine cartilage explants were incubated at either 1% O2 or 20% O2 with either 1 ng/ml 1L-1α. 25 μM MnTE-2-PyP5+ [Mn porphyrin-based catalytic antioxidant, Mn(III) tetrakis(N-ethylpyridinium-2- yl)porphyrin], or 1 ng/ml IL-1 + 25 μM MnTE-2-PyP5+ to decrease peroxynitrite formation. Nitrotyrosine, formed by nitration of tyrosine by peroxynitrite, was measured by immunoblot. Proteoglycan and collagen synthesis and proteoglycan degradation were also determined. Results. IL-1-induced peroxynitrite formation was decreased in 1% O2 as compared to 20% O2. MnTE-2-PyP5+ inhibited IL-1-induced peroxynitrite formation in either 1% O2 or 20% O2. In 1% O2 (but not in 20% O2). Mn porphyrin significantly inhibited IL-1-induced proteoglycan degradation, IL-1 decreased both proteoglycan and collagen II synthesis in cartilage explants in 1% O2 or 20% O 2, but MnTE-2-PyP5+ did not prevent these anti-anabolic effects. MnTE-2-PyP5+ alone caused a significant decrease in collagen synthesis at 20% O2 but not at 1% O2. Conclusion. Our findings show that oxygen tension alters IL-1-induced peroxynitrite formation, which can influence proteoglycan degradation. Oxygen tension may influence the effects of reactive oxygen and nitrogen species on matrix homeostasis.

Original languageEnglish
Pages (from-to)401-407
Number of pages7
JournalJournal of Rheumatology
Issue number2
StatePublished - Feb 2007


  • Articular cartilage
  • Interleukin 1
  • Nitric oxide
  • Oxygen tension
  • Proteoglycan
  • Superoxide dismutase mimetic


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