Plasminogen activator/plasmin system in arthritis and inflammation: Friend or foe?

Urokinase Plasminogen Activator Is a Central Regulator of Macrophage Three-Dimensional Invasion, Matrix Degradation, and Adhesion

“…In addition, we and others demonstrated a dependence on uPA for arthritis development in three systemic mouse models (40,41), supporting the concept that uPA is a major player in inflammatory arthritis (36)(37)(38)42). Whether the proteolytic cascade initiated by uPA is central to macrophage infiltration into and/or efflux out of inflamed tissues (such as the rheumatoid arthritis synovium) remains to be seen.…”

Emerging roles of serine proteinases in tissue turnover in arthritis

“…Targeted deletion of components of the PA/ plasmin cascade has produced conflicting results in murine models (32). In some models, deletion of uPA, plasminogen, or tPA exacerbated arthritis, with increased fibrin accumulation in the joint (31,33), while uPA or plasminogen deletion in other models resulted in only mild disease (31,34,35).…”

“…In some models, deletion of uPA, plasminogen, or tPA exacerbated arthritis, with increased fibrin accumulation in the joint (31,33), while uPA or plasminogen deletion in other models resulted in only mild disease (31,34,35). The reasons for such conflicting observations are unknown, but the differences may be partly attributable to the different pathologies reported in the models used (32). Furthermore, plasmin has contrasting roles in the context of arthritis: plasmin-mediated fibrinolysis is important in maintaining a healthy joint, while plasmin can also contribute directly to ECM proteolysis by cleaving matrix components (glycoproteins, fibronectin, and proteoglycans) or indirectly by proMMP activation and subsequent ECM degradation (36)(37)(38)(39).…”

Proteinase-Activated Receptors and Arthritis

“…Studies with knock-out mice lacking various enzymes involved in the plasminogen activation system have shown differing results. Some mouse strains show resistance to some models of arthritis, but not to other models, whilst other mouse strains exhibit more severe arthritis (discussed in [150]). Therefore, the exact role of this system is still unclear but an imbalance in fibrinolysis is definitely a contributing factor to the pathophysiology of an arthritic joint.…”