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

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.