Induction of vascular endothelial growth factor and matrix metalloproteinase-3 (stromelysin) by interleukin-1 in human articular chondrocytes and synoviocytes

We investigated the effects of interleukin (IL)-1 on vascular endothelial growth factor (VEGF) and matrix metalloproteinase-3 (MMP-3) (stromelysin) secretion from chondrocytes and synoviocytes in different clinical conditions. Specifically, cells obtained from osteoarthritic (OA) (n=7), rheumatoid arthritic (RA) (n=5), and post-traumatic (PT) (n=5) patients were stimulated in vitro with IL-1β in the presence or absence of an IL-1 receptor antagonist (IL-1ra) (anakinra). Levels of secreted MMP-3 and VEGF were measured by enzyme-linked immunosorbent assay. The VEGF mRNA expression was analyzed quantitatively. Interleukin-1 induced both VEGF and MMP-3 secretion from all of the samples tested, and VEGF mRNA expression was also upregulated. Interleukin-1ra significantly suppressed the enhancing effect of IL-1 on MMP-3 and VEGF in both cell types. In conclusion, IL-1 simultaneously induces MMP-3 and VEGF production from chondrocytes and synoviocytes in inflammatory, degenerative, and post-traumatic joints. Therefore, IL-1ra might be beneficial for protection from VEGF-mediated alterations of cartilage metabolism in pathologic and physiologic conditions.