Article
The role of VEGF (Vascular Endothelial Growth Factor) in Osteoarthritis
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Published: | November 11, 2003 |
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Outline
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Objective
In recent studies we have shown, that vascular endothelial growth factor (VEGF) is expressed in osteoarthritic but not in normal cartilage. Aim of this investigation was to analyse the function of VEGF in osteoarthritis (OA).
Methods & results
Immortalized human chondrocytes, which were a model, expressed VEGF and VEGFR-2. As evidenced by real time RT-PCR, VEGFR-2 expression was upregulated by VEGF itself. Stimulation of VEGFR-2 by the ligand resulted in autophosphorylation of the receptor, subsequent phosphorylation of the mitogen-activated protein kinases Erk ½ and finally the activation of the transcription factor AP-1 (activator protein-1) as shown by Western-Blot and electrophoretic mobility shift assay (EMSA). As consequence, VEGF raised the expression of active matrix metalloproteinase-1 (MMP-1) in culture supernatants. Also, chondrocyte proliferation was stimulated by VEGF.
Conclusion
The increased expression of the matrix metalloproteinases leads to a destruction of collagen and the successfully activated MAP-kinase pathway culminates in the expression of proinflammatory cytokines. The more intense proliferation comes along with a reduced coIlagen type II production. In conclusion, VEGF is participated in the osteoarthritic degradation of cartilage.