Cartilage synthesizes the serine protease inhibitor PAI-1: Support for the involvement of serine proteases in cartilage remodeling

The work described here demonstrates the synthesis by human articular cartilage of plasminogen activator inhibitor‐1 (PAI‐1), a potent inhibitor of the serine protease tissue plasminogen activator (tPA). We also present data demonstrating an increase in PAI‐1 messenger ribonucleic acid (mRNA) in chondrocytes exposed to the cytokine interleukin‐1 (IL‐1). Interestingly, this elevation of steady‐state mRNA levels does not appear to result in an increase in synthesis of PAI‐1 protein. Northern blot analysis reveals that of the two mRNA species (3.4 kb, 2.4 kb) previously reported for PAI‐1, only the larger species (3.4 kb) appears to be synthesized by chrondrocytes. Our data demonstrate the IL‐1‐stimulated production by cartilage of tissue plasminogen activator. We also show evidence for the presence of plasminogen in cartilage. A scheme is presented indicating the probable importance of the serine proteases (tPA and plasminogen) and PAI‐1 in cartilage degradation.