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NSAIDs and DMARDS in osteoarthritis: The role of prostaglandin E2 in human osteoarthritic cartilage

Friday 6 November 2009

Prof.dr Floris Lafeber / dr Simon Mastbergen

Cyclooxygenase (COX-2) is an enzyme that is up regulated under the influence of (amongst others) pro-inflammatory cytokines. This enzyme is also present in the cartilage cells of osteoarthritic patients. The turnover of proteoglycans (one of the major components in the cartilage matrix) is disturbed in osteoarthritic cartilage.
Through inhibition of COX-2 by a selective inhibitor there is less prostaglandin E2 (PGE2, the most important product of the COX-2 enzyme) produced. This causes a positive effect on the proteoglycan turnover. The PGE2 receptors (EP1 - EP4) seem to play a role in this process and possibly in the start of osteoarthritis. However, the exact role of PGE2 and its receptors in osteoarthritic cartilage remains unclear.
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 the clinical trial we will look into the expression of COX-1, COX-2, EP2- and EP4-receptor in cartilage and synovium by means of histology and immuno-histochemical techniques.

The aim of this project is to expand the current results en to gain new insights in the role of PGE2 in osteoarthritis on biochemical and microbiological level.

You will contribute to:
- the processing and culturing of human cartilage
- a large diversity of biochemical analyses of the cartilage
- the processing of human cartilage and synovial tissue for histology and immuno-histochemistry
- the set up of further immuno-histochemical analyses of the tissue
- 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

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