Tryptase enhances release of vascular endothelial growth factor from human osteoarthritic chondrocytes.
Clin Exp Rheumatol
; 25(6): 860-5, 2007.
Article
em En
| MEDLINE
| ID: mdl-18173920
ABSTRACT
OBJECTIVE:
A contribution of mast cells and its mediators in the pathogenesis of arthritis has been postulated. We aimed to clarify the role of mast cell-derived serine protease tryptase and proteinase activated receptor (PAR)-2-mediated signaling in chondrocytes.METHODS:
Human articular cartilage specimens were obtained from patients with osteoarthritis (OA), rheumatoid arthritis (RA) and with traumatic fracture without arthritis (PT; as controls) who underwent joint surgery. Isolated chondrocytes were cultured in vitro by monolayer, and confluent cells were incubated with recombinant human lung Beta tryptase or with a PAR-2 agonist peptide. The secreted level of vascular endothelial growth factor (VEGF) in culture supernatant was measured using commercially available ELISA kits, and expression of VEGF mRNA was analyzed using real-time PCR.RESULTS:
The tryptase-stimulated chondrocytes from OA or RA, but not from PT patients, produced significantly higher amount of VEGF in their supernatants. The response was blocked by a G-protein receptor inhibitor pertussis toxin, however, was not reproduced by incubation of cells with the PAR-2 agonist, suggesting a presence of non-PAR-2 dependent signals for the VEGF induction. In addition, actinomycin D and cycloheximide did not exert significant inhibition, indicating a regulation of VEGF release by tryptase.CONCLUSION:
The inflammatory mediator, mast cell-derived protease tryptase may modulate chondrocyte metabolism through induction of VEGF release.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
Condrócitos
/
Fator A de Crescimento do Endotélio Vascular
/
Triptases
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Clin Exp Rheumatol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Japão