Elevated metalloproteinase and tissue inhibitor of metalloproteinase mRNA in human osteoarthritic synovia.
The levels of metalloproteases and inhibitor expression in synovial membranes were measured by analyzing mRNA of collagenase, stromelysin, and tissue inhibitor of metalloproteinase (TIMP-1) in this tissue from 20 healthy persons and 20 patients with osteoarthritis (OA). Our results indicated that while most of the normal synovia expressed TIMP-1 mRNA at low levels, very few expressed metalloproteinase mRNA. In contrast 40% of patients with OA expressed a moderate level of collagenase compared to 55 and 80% cases with considerably elevated stromelysin and TIMP-1 mRNA, respectively. The mRNA expression of collagenase (p < 0.032), stromelysin (p < 0.0001) and TIMP-1 (p < 0.008) was significantly higher in OA than in normals. The greater abundance of stromelysin mRNA relative to collagenase indicates differential regulation of the 2 genes. We also demonstrated an association of IL-1 with metalloproteinase gene expression.
Notre-Dame Hospital Research Center, Department of Medicine, University of Montréal, PQ, Canada.
M
M
Zafarullah
J P
JP
Pelletier
J M
JM
Cloutier
J
J
Martel-Pelletier
D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography; D017364:Collagenases / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D003720:Densitometry; D005260:Female; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics*; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D012016:Reference Values; D013583:Synovial Membrane / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases
D016207:Cytokines; D006023:Glycoproteins; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3