Vascular endothelial growth factor activities on osteoarthritic chondrocytes.
OBJECTIVE
Evaluation of the role of VEGF in cartilage pathophysiology.


METHODS
VEGF release from chondrocytes in the presence of IL-1beta, TGFbeta and IL-10 was detected by immunoassay. VEGF receptor -1 and -2 expression and VEGF ability to modulate caspase -3 and cathepsin B expression were detected by immunohistochemistry on cartilage biopsies and cartilage explants. VEGF effects on chondrocyte proliferation was analysed by a fluorescent dye that binds nucleic acids.


RESULTS
VEGF production by osteoartritis (OA) chondrocytes was significantly reduced by IL-1beta while it was increased in the presence of TGFbeta. Cartilage VEGFR-1 immunostaining was significantly downregulated in 'early' OA patients compared to normal controls (NC). VEGFR-2 expression was negligible both in OA and in NC. VEGF decreased the expression of caspase-3 and cathepsin B, whereas it did not affect proliferation.


CONCLUSIONS
VEGF is able to down-modulate chondrocyte activities related to catabolic events involved in OA cartilage degradation.
Pulsatelli
L
L
Laboratorio di Immunologia e Genetica, Istituti Ortopedici Rizzoli, Bologna, Italy.
Dolzani
P
P
Silvestri
T
T
Frizziero
L
L
Facchini
A
A
Meliconi
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002401:Cathepsin B