Sphingosine-1-phosphate modulates expression of vascular endothelial growth factor in human articular chondrocytes: a possible new role in arthritis
International Journal of Rheumatic Diseases, 08/02/2012
Masuko K et al. – The results suggest that sphingosine–1–phosphate (S1P) may contribute to the regulation of vascular endothelial growth factor (VEGF) expression in human chondrocytes. S1P may therefore play a unique role in the pathophysiology of osteoarthritis by regulating VEGF expression in chondrocytes.Methods
- Human articular cartilage samples were obtained from patients with OA under informed consent.
- Chondrocytes were isolated by an enzymatic procedure, grown in monolayer culture, and then stimulated with S1P in the presence or absence of mitogen-activated protein kinase (MAPK) inhibitors or the Gi protein inhibitor pertussis toxin (PTX).
- VEGF expression and secretion in culture supernatants were analyzed using real-time polymerase chain reaction and enzyme-linked immunosorbent assay.
- Although S1P did not enhance basal secretion of matrix metalloproteinase (MMP)-1 and MMP-13, it stimulated VEGF expression in human articular chondrocytes, both at the messenger RNA and protein levels.
- MAPK inhibitors SB203580 and PD98059 were not effective at suppressing VEGF induction; rather, blocking extracellular signal-regulated kinase (ERK) MAPK enhanced VEGF expression.
- The Gi protein inhibitor PTX partially attenuated S1P-induced VEGF secretion.