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The role of prostaglandin E2 in human osteoarthritic cartilage

Monday 4 May 2009

Dr. F.P.J.G. Lafeber

Project
The research of the department of Rheumatology & Clinical Immunology of the University Medical Center Utrecht mainly focuses on tissue damage in rheumatic diseases, such as cartilage damage in osteoarthritis (OA) and rheumatoid arthritis (RA). Using both clinical and experimental approaches, the final goal of our research is to develop novel therapeutic strategies. The nature of our research is translational; questions raised during clinical treatment are studied in vitro and in animal in vivo models (from bed-side to bench). The other way around, results from the “bench” are translated to the “bed-side”.
Our department has been approved as EULAR Centres of Excellence 2006-2011.
In the case of OA, in which cartilage damage plays a central role, we focus on the stimulation of the intrinsic repair activity of the cartilage tissue. This distinguishes us from many other groups in this field of research, which focus on transplantation of cartilage (precursor) tissue and/or cells or on tissue engineering of cartilage. In this respect we have a significant past performance over the past years (see in pubmed under ‘Lafeber F‘).
Within several lines of our research presently extra input and support is desired.

Communication between prostaglandin E2, EP-recptors and osteoarthritic cartilage
Cyclooxygenase (COX-2) is a enzyme which is upregulated under influence of pro-inflammatory cytokines, among other triggers. This enzyme is also upregulated in degenerated osteoarthritic cartilage. In this cartilage the proteoglycan, turnover as one the most important components in the extracellular matrix of cartilage, is changed. One of the main products of COX-2 is prostaglandin E2 (PGE2). Inhibition of COX-2 by a selective COX-2 inhibitor results in a beneficial effect on the proteoglycan turnover. This indirectly suggests that PGE2 plays a role in the process of osteoarthritis. In addition, there seems also a role for the different recptors of PGE2, the socalled EP1 to EP4 receptors. The exact role of PGE2 and its EP-receptors in human osteoarthritic cartilage is still unclear. The main purpose of the project is the extension of present results and to further clarify the communication between PGE2 and cartilage on a biochemical and microbiological level.

Techniques
Obtaining and culture of human cartilage tissue; biochemical techniques (proteoglycan assays); immunohistochemistry (COX-2 expression, EP-receptors); PGE2 assessment by ELISA

Duration
6 or 9 months

Contact
General info: Floris Lafeber, 088 75 585 21, F.Lafeber@umcutrecht.nl
Detailed info: Joel van Roon, 088 75 597 58, J.vanRoon@umcutrecht.nl

More info
http://www.umcutrecht.nl/subsite/rheumatology-research

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