NDLI: Sphingosine-1-phosphate modulates expression of vascular endothelial growth factor in human articular chondrocytes: a possible new role in arthritis

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Sphingosine-1-phosphate modulates expression of vascular endothelial growth factor in human articular chondrocytes: a possible new role in arthritis

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Sphingosine-1-phosphate modulates expression of vascular endothelial growth factor in human articular chondrocytes: a possible new role in arthritis

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Masuko, Kayo Murata, Minako Beppu, Moroe Nakamura, Hiroshi Kato, Tomohiro Yudoh, Kazuo
Description	Country affiliation: Japan Author Affiliation: Masuko K ( Department of Biochemistry, St. Marianna University School of Medicine, Kanagawa, Japan. k_msk@mac.com)
Abstract	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.
File Format	HTM / HTML
ISSN	17561841
Issue Number	4
Volume Number	15
e-ISSN	1756185X
Journal	International Journal of Rheumatic Diseases
Language	English
Publisher	Wiley
Publisher Date	2012-08-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Rheumatology Chondrocytes Drug Effects Gene Expression Lysophospholipids Pharmacology Osteoarthritis Metabolism Sphingosine Analogs & Derivatives Vascular Endothelial Growth Factor A Genetics Aged Cartilage, Articular Cytology Cells, Cultured Pathology Drug Interactions Enzyme Inhibitors Female Fingolimod Hydrochloride Flavonoids Humans Imidazoles Immunosuppressive Agents Male Mitogen-activated Protein Kinases Antagonists & Inhibitors Diagnosis Pertussis Toxin Propylene Glycols Pyridines Rna, Messenger Journal Article
Content Type	Text
Resource Type	Article
Subject	Rheumatology

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