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Open Access 01-12-2011 | Research article

The Immunosuppressant FTY720 (Fingolimod) enhances Glycosaminoglycan depletion in articular cartilage

Authors: Martin H Stradner, Hannes Angerer, Thomas Ortner, Florentine C Fuerst, Daniela Setznagl, Marie-Luise Kremser, Josef Hermann, Winfried B Graninger

Published in: BMC Musculoskeletal Disorders | Issue 1/2011

Abstract

Background

FTY720 (Fingolimod) is a novel immunosuppressive drug investigated in clinical trials for organ transplantation and multiple sclerosis. It acts as a functional sphingosine-1-phosphate (S1P) receptor antagonist, thereby inhibiting the egress of lymphocytes from secondary lymphoid organs. As S1P is able to prevent IL-1beta induced cartilage degradation, we examined the direct impact of FTY720 on cytokine induced cartilage destruction.

Methods

Bovine chondrocytes were treated with the bioactive phosphorylated form of FTY720 (FTY720-P) in combination with IL-1beta or TNF-alpha. Expression of MMP-1,-3.-13, iNOS and ADAMTS-4,-5 and COX-2 was evaluated using quantitative real-time PCR and western blot. Glycosaminoglycan depletion from cartilage explants was determined using a 1,9-dimethylene blue assay and safranin O staining.

Results

FTY720-P significantly reduced IL-1beta and TNF-alpha induced expression of iNOS. In contrast FTY720-P increased MMP-3 and ADAMTS-5 mRNA expression. Furthermore depletion of glycosaminoglycan from cartilage explants by IL-1beta and TNF-alpha was significantly enhanced by FTY720-P in an MMP-3 dependent manner.

Conclusions

Our results suggest that FTY720 may enhance cartilage degradation in pro-inflammatory environment.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/12/279/prepub

Title: The Immunosuppressant FTY720 (Fingolimod) enhances Glycosaminoglycan depletion in articular cartilage
Authors: Martin H Stradner
Hannes Angerer
Thomas Ortner
Florentine C Fuerst
Daniela Setznagl
Marie-Luise Kremser
Josef Hermann
Winfried B Graninger
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: BMC Musculoskeletal Disorders / Issue 1/2011
Electronic ISSN: 1471-2474
DOI: https://doi.org/10.1186/1471-2474-12-279

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The Immunosuppressant FTY720 (Fingolimod) enhances Glycosaminoglycan depletion in articular cartilage

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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