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 chondrocytes. 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.
Treadwell
B V
BV
Orthopaedic Research Laboratories, Massachusetts General Hospital, Boston 02114.
Pavia
M
M
Towle
C A
CA
Cooley
V J
VJ
Mankin
H J
HJ
D015152:Blotting, Northern; D002356:Cartilage / Q000201:enzymology*; D004586:Electrophoresis; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D010958:Plasminogen / Q000032:analysis / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000378:metabolism*; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis*
D007375:Interleukin-1; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D010958:Plasminogen; D010959:Tissue Plasminogen Activator