Recombinant human protease nexin-1 prevents articular cartilage-degradation in the rabbit

Cartilage degradation is mediated by activated matrix metalloproteinases (MMP). Since the plasmin/plasminogen cascade may activate latent MMP during cartilage catabolism, we determined if protease nexin-1 (PN-1), an inhibitor of plasminogen, plasmin, and urokinase could prevent cartilage degradation. Using a rabbit model, we induced cartilage glycosaminoglycan (GAG) loss by intraarticular (IA) injection of IL-1 beta and bFGF. PN-1 was given IA for 4 days, once before IL-1 beta/bFGF and daily for 3 days. Three days after IL-1 beta/bFGF, we determined GAG loss. PN-1 significantly inhibited GAG loss at 2.8, 2.5 mg, and 2.0 mg/knee (p < 0.03). These data suggest the role of the plasmin/plasminogen enzymatic cascade in the cartilage catabolism that occurs during IL-1-induced inflammation and demonstrates the potential of PN-1 to prevent cartilage degradation.