Plasminogen activation/plasmin in rheumatoid arthritis: matrix degradation and more

Rheumatoid arthritis (RA) is one of the most common and most debilitating joint diseases, producing high personal, social, and economic costs.(1,2) Patients with RA suffer pain and functional losses, often followed by disability and premature death. Although the etiology of RA is unknown, substantial efforts have been directed toward studying the transition of the joint from normal to diseased. The maintenance of normal joint architecture and function requires equilibrium between the synthesis and degradation of the specialized extracellular matrices that make up bone, cartilage, and tendons. In RA, the balance of tissue remodeling is disturbed,(3) and excessive proteolytic degradation of the joint matrices leads to joint destruction.(4,5) The early phase of RA is characterized by the infiltration of immune and inflammatory cells into the synovium and by hyperplasia of the fibroblasts in the synovial lining. This leads to pannus formation, cartilage breakdown, and eventual bone destruction.(1,2) Through the use of an experimental mouse model of RA, Li and colleagues(6) have implicated plasmin as an essential component of the early phase of RA, as reported in this issue of The American Journal of Pathology.