Document Detail

Sphingosine-1-phosphate modulates expression of vascular endothelial growth factor in human articular chondrocytes: a possible new role in arthritis.
MedLine Citation:
PMID:  22898216     Owner:  NLM     Status:  MEDLINE    
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 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.
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.
Kayo Masuko; Minako Murata; Moroe Beppu; Hiroshi Nakamura; Tomohiro Kato; Kazuo Yudoh
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Publication Detail:
Type:  Journal Article     Date:  2012-07-16
Journal Detail:
Title:  International journal of rheumatic diseases     Volume:  15     ISSN:  1756-185X     ISO Abbreviation:  Int J Rheum Dis     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-17     Completed Date:  2013-01-15     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  101474930     Medline TA:  Int J Rheum Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  366-73     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors International Journal of Rheumatic Diseases © 2012 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.
Department of Biochemistry, St. Marianna University School of Medicine, Kanagawa, Japan.
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MeSH Terms
Cartilage, Articular / cytology
Cells, Cultured
Chondrocytes / drug effects*,  metabolism,  pathology
Drug Interactions
Enzyme Inhibitors / pharmacology
Flavonoids / pharmacology
Gene Expression / drug effects*
Imidazoles / pharmacology
Immunosuppressive Agents / pharmacology
Lysophospholipids / pharmacology*
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Osteoarthritis / diagnosis,  genetics,  metabolism*
Pertussis Toxin / pharmacology
Propylene Glycols / pharmacology
Pyridines / pharmacology
RNA, Messenger / metabolism
Sphingosine / analogs & derivatives*,  pharmacology
Vascular Endothelial Growth Factor A / genetics*,  metabolism*
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Enzyme Inhibitors; 0/Flavonoids; 0/Imidazoles; 0/Immunosuppressive Agents; 0/Lysophospholipids; 0/Propylene Glycols; 0/Pyridines; 0/RNA, Messenger; 0/SB 203580; 0/VEGFA protein, human; 0/Vascular Endothelial Growth Factor A; 123-78-4/Sphingosine; 26993-30-6/sphingosine 1-phosphate; 3QN8BYN5QF/fingolimod; EC Toxin; EC Protein Kinases

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