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

BMC Musculoskeletal Disorders

Research Article

Hannes Angerer¹  Marie-Luise Kremser¹  Florentine C Fuerst¹  Josef Hermann¹  Thomas Ortner¹  Daniela Setznagl¹  Winfried B Graninger¹  Martin H Stradner¹ 

[1] Division of Rheumatology and Immunology, Medical University of Graz, Austria;

关键词: chondrocyte;    fingolimod;    FTY720;    interleukin-1β;    tumor necrosis factor-α;    inducible nitric oxide synthase;    glycosaminoglycan;   

DOI  :  10.1186/1471-2474-12-279

 received in 2011-05-30, accepted in 2011-12-12,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundFTY720 (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.MethodsBovine 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.ResultsFTY720-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.ConclusionsOur results suggest that FTY720 may enhance cartilage degradation in pro-inflammatory environment.

【 授权许可】

CC BY   
© Stradner et al; licensee BioMed Central Ltd. 2011