Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Stradner, MH; Angerer, H; Ortner, T; Fuerst, FC; Setznagl, D; Kremser, ML; Hermann, J; Graninger, WB.
The immunosuppressant FTY720 (fingolimod) enhances glycosaminoglycan depletion in articular cartilage.
BMC Musculoskelet Disord. 2011; 12(11):279-279
Doi: 10.1186/1471-2474-12-279
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- Führende Autor*innen der Med Uni Graz
- Stradner Martin Helmut
- Co-Autor*innen der Med Uni Graz
- Angerer Hannes
- Graninger Winfried
- Hermann Josef
- Kremser Maria-Luise
- Moazedi-Fürst Florentine
- Ortner Thomas
- Peischler Daniela
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- Abstract:
- 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. 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. 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. Our results suggest that FTY720 may enhance cartilage degradation in pro-inflammatory environment.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cartilage, Articular - drug effects
- Cartilage, Articular - enzymology
- Cartilage, Articular - metabolism
- Cattle -
- Cells, Cultured -
- Chondrocytes - drug effects
- Chondrocytes - metabolism
- Chondrocytes - pathology
- Fingolimod Hydrochloride -
- Glycosaminoglycans - antagonists & inhibitors
- Glycosaminoglycans - metabolism
- Immunosuppressive Agents - toxicity
- Interleukin-1beta - physiology
- Matrix Metalloproteinase 13 - biosynthesis
- Matrix Metalloproteinase 3 - biosynthesis
- Nitric Oxide Synthase Type II - genetics
- Nitric Oxide Synthase Type II - metabolism
- Propylene Glycols - toxicity
- Sphingosine - analogs & derivatives
- Sphingosine - toxicity
- Tumor Necrosis Factor-alpha - physiology
- Find related publications in this database (Keywords)
- chondrocyte
- fingolimod
- FTY720
- interleukin-1 beta
- tumor necrosis factor-alpha
- inducible nitric oxide synthase
- glycosaminoglycan