PMID- 7699636
OWN - NLM
STAT- MEDLINE
DCOM- 19950504
LR  - 20131121
IS  - 0315-162X (Print)
IS  - 0315-162X (Linking)
VI  - 21
IP  - 12
DP  - 1994 Dec
TI  - Control of the chondrocyte fibrinolytic balance by the drug piroxicam: relevance 
      to the osteoarthritic process.
PG  - 2322-8
AB  - OBJECTIVE: Since the plasminogen activator [PA/plasminogen activator inhibitor 
      (PAI) system is believed to be involved in a breakdown of articular cartilage in 
      osteoarthritis (OA), we studied the modulation of single components of the 
      fibrinolytic system (urokinase-type plasminogen activator, u-PA; plasminogen 
      activator inhibitor-1, PAI-1; the surface receptor for u-PA, u-PAR) in human 
      chondrocytes in the presence of piroxicam. METHODS: The drug was added to the 
      chondrocyte culture medium either directly or by supplementing chondrocyte 
      cultures with synovial fluid (SF) from patients with OA treated with piroxicam. 
      We have shown u-PAR M(r) 55000 Da on human chondrocytes in suspension culture by 
      cross linking chondrocyte lysates with 125I-labelled amino-terminal fragment 
      (ATF) of human u-PA, which frames the sequence that specifically interacts with 
      u-PAR. RESULTS: Such receptors decrease upon incubation of chondrocytes with 
      piroxicam or with SF from patients treated with piroxicam. The culture medium of 
      treated chondrocytes showed decreased fibrinolytic activity when compared with 
      untreated controls, while PAI activity was increased in both SF chondrocyte 
      culture medium following piroxicam treatment. At the same time, internalization 
      of u-PA/u-PAR complexes increased after incubation of chondrocytes with piroxicam 
      or PAI-1 rich SF. CONCLUSION: Our results indicate that the drug induces the 
      surface clearance u-PAR by internalization of u-PA/PAI-/u-PAR complexes. Thus 
      piroxicam reduces both the soluble fibrinolytic activity of human chondrocytes 
      (increase of PAI activity and decrease of released u-PA) and the cell associated 
      u-PA activity (clearance of u-PAR by internalization). The drug dependent changes 
      in the fibrinolytic system suggest that piroxicam may be useful in preventing or 
      limiting perilacunar cartilage damage in OA.
FAU - Fibbi, G
AU  - Fibbi G
AD  - Istituto di Patologia Generale, Universita di Firenze, Italy.
FAU - Serni, U
AU  - Serni U
FAU - Matucci, A
AU  - Matucci A
FAU - Mannoni, A
AU  - Mannoni A
FAU - Pucci, M
AU  - Pucci M
FAU - Anichini, E
AU  - Anichini E
FAU - Del Rosso, M
AU  - Del Rosso M
LA  - eng
PT  - Journal Article
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
RN  - 0 (PLAUR protein, human)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
RN  - 13T4O6VMAM (Piroxicam)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
SB  - IM
MH  - Autoradiography
MH  - Cartilage, Articular/drug effects/*metabolism/pathology
MH  - Cells, Cultured
MH  - Fibrinolysis/*drug effects
MH  - Humans
MH  - Osteoarthritis/*drug therapy/metabolism/pathology
MH  - Piroxicam/analysis/*pharmacology/therapeutic use
MH  - Plasminogen Activator Inhibitor 1/metabolism
MH  - Receptors, Cell Surface/metabolism
MH  - Receptors, Urokinase Plasminogen Activator
MH  - Synovial Fluid/chemistry
MH  - Urokinase-Type Plasminogen Activator/metabolism
EDAT- 1994/12/01 00:00
MHDA- 1994/12/01 00:01
CRDT- 1994/12/01 00:00
PHST- 1994/12/01 00:00 [pubmed]
PHST- 1994/12/01 00:01 [medline]
PHST- 1994/12/01 00:00 [entrez]
PST - ppublish
SO  - J Rheumatol. 1994 Dec;21(12):2322-8.