Dr. Graninger has received consulting fees, speaking fees, and/or honoraria from Roche, Bristol-Myers Squibb, MSD, and Pfizer (less than $10,000 each).
Sphingosine 1-Phosphate Counteracts the Effects of Interleukin-1β in Human Chondrocytes
Article first published online: 26 JUL 2013
© 2013 The Authors. Arthritis & Rheumatism is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Arthritis & Rheumatism
Volume 65, Issue 8, pages 2113–2122, August 2013
How to Cite
Stradner, M. H., Gruber, G., Angerer, H., Huber, V., Setznagl, D., Kremser, M.-L., Moazedi-Fürst, F. C., Windhager, R. and Graninger, W. B. (2013), Sphingosine 1-Phosphate Counteracts the Effects of Interleukin-1β in Human Chondrocytes. Arthritis & Rheumatism, 65: 2113–2122. doi: 10.1002/art.37989
- Issue published online: 26 JUL 2013
- Article first published online: 26 JUL 2013
- Accepted manuscript online: 10 MAY 2013 01:57PM EST
- Manuscript Accepted: 18 APR 2013
- Manuscript Received: 7 MAY 2012
- Austrian Science Fund (FWF). Grant Numbers: P 21065-B02, J 3189-B11
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.