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NSAIDs and DMARDS in osteoarthritis: mRNA levels of COX and EP receptors in cartilage and synovium of OA patients

Friday 6 November 2009

Prof.dr Floris Lafeber / dr Simon Mastbergen

Osteoarthritis is a degenerative joint disease that is characterized with progressive damage of the articular cartilage, change in the subchondral bone, osteofytes and possible inflammation of the synovium. A cure does not exist and treatment that is often given to patients with osteoarthritis is non-steroidal anti-inflammatory drugs (NSAIDs) to relieve pain and to inhibit inflammation.

Recent in vitro research has shown that celecoxib, a selective COX-2 inhibitor (second generation NSAIDs), has a positive effect on articular cartilage and possibly even induces cartilage repair.

At this moment there is a clinical trial running in collaboration with the Sint Franciscus Gasthuis in Rotterdam to evaluate the effects of a 4 week treatment with celecoxib (selective COX-2 inhibitor) in patients with severe knee osteoarthritis in comparison with the non-selective NSAID naproxen or no treatment.

In the material collected in this trial we will measure the levels of gene expression of factors involved in osteoarthritis like COX-1/COX-2 with mRNA analysis. We will also determine what the influence of medication is on the gene expression. Furthermore we will evaluate the mechanism of osteoarthritis, amongst which is the expression of the so called EP-receptors.

The aim of this project is the development and execution of mRNA analyses of human cartilage and synovial tissue collected during the clinical trial. For the further evaluation of the underlying mechanisms additional (in vitro) experiments will be performed with human cartilage cultures.

You will contribute to:
- the processing and culturing of human cartilage and synovial tissue cultures
- the isolation of RNA from these tissues
- mRNA analysis methods with amongst others Northern blots
- the base of a publication

6 or 9 months

Dr Simon Mastbergen, S.Mastbergen@umcutrecht.nl, 088 75 597 58
Prof.dr Floris Lafeber, F.Lafeber@umcutrecht.nl, 088 75 585 21