Human urinary trypsin inhibitor inhibits the activation of pro-matrix metalloproteinases and proteoglycans release in rabbit articular cartilage.
Treatment of primary cultured chondrocytes from rabbit articular cartilage with interleukin-1 (IL-1)alpha and plasminogen induced the production of pro-matrix metalloproteinase 1 (proMMP-1/interstitial collagenase), proMMP-3 (stromelysin 1) and proMMP-9 (gelatinase B), as well as their active forms. Human urinary trypsin inhibitor (UTI), a multipotent inhibitor of serine proteases, including plasmin inhibited the activation of proMMP-1, proMMP-3 and proMMP-9 when added to the culture medium together with IL-1alpha and plasminogen, in a dose-dependent manner. Moreover, UTI inhibited the release of proteoglycans induced by IL-1alpha and plasminogen from rabbit articular cartilage explants. These findings strongly suggest that UTI inhibits the destruction of articular cartilage induced by plasmin and/or MMPs. Thus, UTI probably exert an anti-osteoarthritic action via inactivation of proMMPs.
Hashimoto
K
K
Biosciences Research Laboratory, Mochida Pharmaceutical Co., Ltd., Tokyo, Japan.
Nagao
Y
Y
Kato
K
K
Mori
Y
Y
Ito
A
A
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D010960:Plasminogen Activators / Q000378:metabolism; D011509:Proteoglycans / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D014361:Trypsin Inhibitors / Q000494:pharmacology
D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D011509:Proteoglycans; D014361:Trypsin Inhibitors; D010960:Plasminogen Activators; D005341:Fibrinolysin; D017364:Collagenases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; C028665:urinastatin