title: Effects of nonsteroidal anti-inflammatory drugs on the expression of urokinase plasminogen activator and inhibitor and gelatinases in the early osteoarthritic knee of humans.
abstract: OBJECTIVE
  The purpose of this study was to examine the ex vivo effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the expression of urokinase-type plasminogen activator (u-PA), PA inhibitor-1 (PAI-1) and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] in the early knee osteoarthritis (OA) of humans.
  
  
  METHODS
  Samples of articular cartilage, meniscus and synovium of OA patients were obtained and cultured ex vivo in the presence or absence of NSAIDs (diclofenac sodium, nimesulide, celecoxib, valdecoxib, rofecoxib and etoricoxib).
  
  
  RESULTS
  Gelatin zymography showed that all NSAIDs generally decreased MMP-2 secretion in chondral, meniscal and synovial cultures as well as MMP-9 production in meniscal and synovial cultures. ELISA showed the inhibitions of u-PA secretion in chondral cultures by diclofenac and rofecoxib as well as in chondral and synovial cultures by nimesulide, celecoxib and etoricoxib at 48 h. On PAI-1 secretion, rofecoxib in synovial cultures and diclofenac, nimesulide, celecoxib and etoricoxib in chondral and synovial cultures had significantly suppressive effects at 48 h.
  
  
  CONCLUSIONS
  This study clearly demonstrates that NSAIDs can down-regulate the PA/plasmin system and gelatinases expression during the early stage of knee OA, thereby possibly affect the structural progression of the disease. This inhibition seems to be independent selection of COX-1 and COX-2.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Ko-Huang
authors.initials: KH
authors.lastname: Lue
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
authors.forename: I-Chang
authors.initials: IC
authors.lastname: Chang
authors.forename: Ko-Hsiu
authors.initials: KH
authors.lastname: Lu
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D007719:Knee Joint / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D013583:Synovial Membrane / Q000201:enzymology / Q000378:metabolism; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9