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SHR Neuro Cancer Cardio Lipid Metab Microb

Stradner, MH; Gruber, G; Angerer, H; Huber, V; Setznagl, D; Kremser, ML; Moazedi-Fürst, FC; Windhager, R; Graninger, WB.
Sphingosine 1-phosphate counteracts the effects of interleukin-1β in human chondrocytes.
Arthritis Rheum. 2013; 65(8):2113-2122 Doi: 10.1002/art.37989 [OPEN ACCESS]
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Leading authors Med Uni Graz: Stradner Martin Helmut
Co-authors Med Uni Graz: Angerer Hannes; Graninger Winfried; Gruber Gerald; Kremser Maria-Luise; Moazedi-Fürst Florentine; Peischler Daniela; Windhager Reinhard
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Abstract:: The lipid mediator sphingosine 1-phosphate (S1P) is found in the synovial fluid of osteoarthritis (OA) patients. S1P protects bovine cartilage by counteracting the effects of interleukin-1β (IL-1β). This study was undertaken to examine the interaction of S1P and IL-1β in human OA chondrocytes. Human cartilage was obtained from patients undergoing total knee joint replacement. Chondrocytes were cultured in monolayer and treated with IL-1β and S1P. Expression of S1P receptor subtypes and genes involved in cartilage degradation was evaluated using real-time polymerase chain reaction, immunohistochemistry, and Western blotting. S1P signaling was evaluated using inhibitors of S1P receptors and small interfering RNA (siRNA) knockdown of the S1P2 receptor. Phosphorylation of MAP kinases and NF-κB in response to IL-1β and S1P was detected by Western blotting. S1P2 was identified as the most prevalent S1P receptor subtype in human OA cartilage and chondrocytes in vitro. S1P reduced expression of inducible nitric oxide synthase (iNOS) in IL-1β-treated chondrocytes. Reduction of ADAMTS-4 and matrix metalloproteinase 13 expression by S1P correlated with S1P2 expression. Pharmacologic inhibition of the S1P2 receptor, but not the S1P1 and S1P3 receptors, abrogated the inhibition of iNOS expression. Similar results were observed using siRNA knockdown. S1P signaling inhibited IL-1β-induced phosphorylation of p38 MAPK. In human chondrocytes, S1P reduces the induction of catabolic genes in the presence of IL-1β. Activation of the S1P2 receptor counteracts the detrimental phosphorylation of p38 MAPK by IL-1β. © 2013 The Authors. Arthritis & Rheumatism is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.
Find related publications in this database (using NLM MeSH Indexing): ADAM Proteins - metabolism; ADAMTS4 Protein -; Cartilage, Articular - drug effects; Cartilage, Articular - metabolism; Cartilage, Articular - pathology; Cells, Cultured -; Chondrocytes - drug effects; Chondrocytes - metabolism; Chondrocytes - pathology; Drug Antagonism -; Gene Knockdown Techniques -; Gene Silencing -; Humans -; Interleukin-1beta - metabolism; Interleukin-1beta - pharmacology; Lysophospholipids - pharmacology; Matrix Metalloproteinase 13 - metabolism; NF-kappa B - metabolism; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - metabolism; Phosphorylation -; Procollagen N-Endopeptidase - metabolism; RNA, Small Interfering - genetics; Receptors, Lysosphingolipid - genetics; Receptors, Lysosphingolipid - metabolism; Signal Transduction -; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; Sphingosine-1-Phosphate Receptors -; p38 Mitogen-Activated Protein Kinases - metabolism

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