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Biochemical interaction between subchondral bone and cartilage in osteoarthritis

Friday 6 November 2009

Prof.dr Floris Lafeber / dr Simon Mastbergen

Osteoarthritis (OA) is a degenerative joint disease primarily characterized by progressive damage of articular cartilage, but also other tissues are affected in the process of OA. Changes in subchondral bone are one of the most prominent. Bone is a rich source of mediators that are known to affect cartilage (growth factors, enzymes, etc). Evidence supports that crosstalk between bone and cartilage during OA is possible. Thus, a changed turnover of bone during OA could have its effect on cartilage. Indirect support of interaction between bone and cartilage in the (repair) process of OA is also obtained from clinical practice. Treatments such as joint distraction and osteotomy, both assumed beneficial for cartilage, are accompanied by huge bone changes induced by the treatment itself. Also treatments aimed specific at bone (bisphosphonates) can be beneficial for OA cartilage. This raises the question whether, in addition to mechanical influences, also chemical interactions between bone and cartilage contribute to (repair) processes in OA. At present, there is no decisive information on the molecules and interactions involved in this process. Gaining more knowledge is of importance since attempts for structure modifying treatment of OA, presently primarily focused at cartilage repair, has not yet been proven to be effective. It might well be that treatment of bone in addition to cartilage is indicated to successfully treat OA.

The present proposal aims on ways to prevent progression of osteoarthritis by influencing the bone-component in the pathogenesis of OA. We focus on the following questions:
1. Are effects from normal and OA bone(cells) on cartilage different?
2. Which mediators are involved in the effects of bone on cartilage?
3. Are these mediators detectable in patients with OA?
4. Can bone cells or their mediators be influenced in such a way that they contribute to cartilage repair?

As a student you will be involved in :
- Culture of cartilage and bonecells (osteoblasts) both separate and in cocultures.
- A large array of biochemical and histochemical analyses of cartilage and bone such as immunohistochemistry, in vitro labelling, ELISA’s, mRNA assays among other techniques.
- Preparing 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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