Animal models of arthritis in NOS2-deficient mice

Objective: To study the role of nitric oxide (NO) in cartilage destruction in murine models of arthritis and osteoarthritis. Methods: Joint inflammation was induced in the knee joint by intraarticular injection of Zymosan. Osteoarthritis was induced by local injection of bacterial collagenase, causing joint instability. The effect of NO deficiency was studied by comparing the effects in normal mice and mice with genetically disrupted NOS2 (inducible NO synthase). Impact on articular cartilage was evaluated by histology and measurement of chondrocyte 35S-proteoglycan synthesis. Results: NOS2 deficiency prevented chondrocyte proteoglycan synthesis inhibition in the arthritic cartilage and restored normal responsiveness to IGF-I. Net cartilage proteoglycan depletion was markedly reduced in the absence of NOS2, although inflammation was hardly affected. Osteoarthritic joint pathology was also significantly reduced, including diminished cartilage lesions and osteophyte formation. Conclusion: NO plays a major role in cartilage damage in both arthritic and osteoarthritic conditions.