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Control of the chondrocyte fibrinolytic balance by the drug piroxicam: relevance to the osteoarthritic process.
J Rheumatol. 1994 Dec; 21(12):2322-8.JR

Abstract

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.

Authors+Show Affiliations

Fibbi G
Istituto di Patologia Generale, Università di Firenze, Italy.
Serni U
No affiliation info available
Matucci A
No affiliation info available
Mannoni A
No affiliation info available
Pucci M
No affiliation info available
Anichini E
No affiliation info available
Del Rosso M
No affiliation info available

MeSH

AutoradiographyCartilage, ArticularCells, CulturedFibrinolysisHumansOsteoarthritisPiroxicamPlasminogen Activator Inhibitor 1Receptors, Cell SurfaceReceptors, Urokinase Plasminogen ActivatorSynovial FluidUrokinase-Type Plasminogen Activator

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7699636

Citation

Fibbi, G, et al. "Control of the Chondrocyte Fibrinolytic Balance By the Drug Piroxicam: Relevance to the Osteoarthritic Process." The Journal of Rheumatology, vol. 21, no. 12, 1994, pp. 2322-8.
Fibbi G, Serni U, Matucci A, et al. Control of the chondrocyte fibrinolytic balance by the drug piroxicam: relevance to the osteoarthritic process. J Rheumatol. 1994;21(12):2322-8.
Fibbi, G., Serni, U., Matucci, A., Mannoni, A., Pucci, M., Anichini, E., & Del Rosso, M. (1994). Control of the chondrocyte fibrinolytic balance by the drug piroxicam: relevance to the osteoarthritic process. The Journal of Rheumatology, 21(12), 2322-8.
Fibbi G, et al. Control of the Chondrocyte Fibrinolytic Balance By the Drug Piroxicam: Relevance to the Osteoarthritic Process. J Rheumatol. 1994;21(12):2322-8. PubMed PMID: 7699636.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Control of the chondrocyte fibrinolytic balance by the drug piroxicam: relevance to the osteoarthritic process. AU - Fibbi,G, AU - Serni,U, AU - Matucci,A, AU - Mannoni,A, AU - Pucci,M, AU - Anichini,E, AU - Del Rosso,M, PY - 1994/12/1/pubmed PY - 1994/12/1/medline PY - 1994/12/1/entrez SP - 2322 EP - 8 JF - The Journal of rheumatology JO - J Rheumatol VL - 21 IS - 12 N2 - 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. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/7699636/Control_of_the_chondrocyte_fibrinolytic_balance_by_the_drug_piroxicam:_relevance_to_the_osteoarthritic_process_ L2 - https://medlineplus.gov/osteoarthritis.html DB - PRIME DP - Unbound Medicine ER -