title: Influence of oxygen tension on interleukin 1-induced peroxynitrite formation and matrix turnover in articular cartilage.
abstract: 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 (OONO-), 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 IL-1alpha, 25 microM MnTE-2-PyP5+ [Mn porphyrin-based catalytic antioxidant, Mn(III) tetrakis(N-ethylpyridinium-2-yl)porphyrin], or 1 ng/ml IL-1 + 25 microM 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% O2, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Division of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cernanec
authors.forename: J Brice
authors.initials: JB
authors.lastname: Weinberg
authors.forename: Ines
authors.initials: I
authors.lastname: Batinic-Haberle
authors.forename: Farshid
authors.initials: F
authors.lastname: Guilak
authors.forename: Beverley
authors.initials: B
authors.lastname: Fermor
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000096:biosynthesis; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D053582:Interleukin-1alpha / Q000494:pharmacology*; D008665:Metalloporphyrins / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D013552:Swine; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004338:Drug Combinations; D053582:Interleukin-1alpha; D008665:Metalloporphyrins; D011509:Proteoglycans; C431023:manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D003094:Collagen; D010100:Oxygen