Effect of NOS2 gene deficiency on the development of autoantibody mediated arthritis and subsequent articular cartilage degeneration

Hisayoshi Kato, Keiichiro Nishida, Aki Yoshida, Itsuro Takada, Cherie McCown, Masatsugu Matsuo, Takuro Murakami, Hajime Inoue

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19 Citations (Scopus)

Abstract

Objective. To determine the effect of NOS2 gene deletion on articular cartilage degradation in autoantibody mediated arthritis (AMA). Methods. Female C57BL/6Ai-[ko] NOS2 N5 (NOS2-/-) mice (7-8 weeks old) and the counterpart C57/B16 Crj mice (wild-type, WT) were studied. Arthritis was induced by intraperitoneal injection of 4 mg of an arthritogenic cocktail of 4 monoclonal antibodies raised against type II collagen twice on Day 0 and Day 1 followed by intraperitoneal injection of 50 μg of lipopolysaccharide on Day 2. Individual limbs were scored for arthritis in 4 grades; the total maximum score per mouse was 16. Femoral condyles and tibial plateaus of both knee joints were collected on Day 15 for immunohistological studies on nitrotyrosine and matrix metalloproteinase (MMP)-3 and -9. DNA fragmentation in chondrocytes was detected by the nick-end labeling (TUNEL) method. Blood was also collected on Day 15 to determine serum levels of nitrite/nitrate and interleukin 1β (IL-1β). Results. Both NOS2-/- and WT mice with AMA developed clinically apparent arthritis. In WT mice, the arthritis progressed rapidly and reached the peak score 11.4 ± 2.9 on Day 12, whereas the arthritis in NOS2-/- mice was milder and the peak score was 7.7 ± 2.8 on Day 13 (p < 0.05). The serum nitrite/nitrate levels, histological grades of articular cartilage degradation, and numbers of apoptotic chondrocytes and nitrotyrosine positive chondrocytes were significantly lower in NOS2-/- mice with AMA than in WT mice with AMA. Conversely, significant differences were not observed in MMP-3 or -9 expression in chondrocytes, or in serum IL-1β levels between these 2 groups of mice. Conclusion. NOS2 gene deletion did not affect the inflammatory responses, but reduced the cartilage degradation.

Original languageEnglish
Pages (from-to)247-255
Number of pages9
JournalJournal of Rheumatology
Volume30
Issue number2
Publication statusPublished - Feb 1 2003

Keywords

  • Autoantibody mediated arthritis
  • Cartilage
  • NOS2
  • Nitric oxide

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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  • Cite this

    Kato, H., Nishida, K., Yoshida, A., Takada, I., McCown, C., Matsuo, M., Murakami, T., & Inoue, H. (2003). Effect of NOS2 gene deficiency on the development of autoantibody mediated arthritis and subsequent articular cartilage degeneration. Journal of Rheumatology, 30(2), 247-255.