Premium
Sphingosine‐1‐phosphate modulates expression of vascular endothelial growth factor in human articular chondrocytes: a possible new role in arthritis
Author(s) -
Masuko Kayo,
Murata Minako,
Beppu Moroe,
Nakamura Hiroshi,
Kato Tomohiro,
Yudoh Kazuo
Publication year - 2012
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/j.1756-185x.2012.01756.x
Subject(s) - vascular endothelial growth factor , mapk/erk pathway , angiogenesis , medicine , microbiology and biotechnology , sphingosine kinase 1 , kinase , protein kinase a , small interfering rna , vascular endothelial growth factor a , arthritis , cancer research , matrix metalloproteinase , sphingosine 1 phosphate , sphingosine , transfection , biology , cell culture , receptor , vegf receptors , genetics
Aim Although sphingosine‐1‐phosphate (S1P) is suggested to have an important role in arthritis, its function in chondrocytes remains unknown. In contrast, vascular endothelial growth factor ( VEGF ) has been speculated to contribute to the pathogenesis of osteoarthritis ( OA ), most likely by regulating angiogenesis. We here investigated the in vitro effect of S1P on VEGF expression in human articular chondrocytes from OA patients. 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. Results 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 SB 203580 and PD 98059 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. Conclusion Our results suggest that S1P may contribute to the regulation of VEGF expression in human chondrocytes. S1P may therefore play a unique role in the pathophysiology of OA by regulating VEGF expression in chondrocytes.