Identification of important interactions between subchondral bone ...

CHAPTER 7: PAPER IV
mediated aggrecan degradation with GM6001 in the MMP buffer, demonstrating that the human
OA cartilage is not depleted for metalloproteinases (table 1).
Fig. 2. Schematic overview of the masking effect of endogenous
proteases in human OA cartilage. The MMP-mediated neoepitope,
AGNx-II, is further processed by cysteine proteases. Thus,
Inhibition of cysteine proteases result in increased AGNx-II.
Several studies by our group have shown that a combination of the cytokines, OSM + TNF-α,
induce a damaging effect on cartilage by increasing the production of proteases, e.g. aggrecanases
and MMPs 3,4 . This induces a shift from normal turnover towards an uneven turnover - resulting
in excessive protein degradation. In the present study, we pre-stimulated normal bovine cartilage
explants with the cytokines to induce a catabolic system that resemble human OA cartilage
regarding the proteases. This would allow us to have a system representing the proteases in
normal and diseased cartilage, from the same cartilage explant. The cartilage explant pre-
stimulated with cytokines for 4 days increased the aggrecanase-mediated aggrecan degradation,
whereas the cartilage pre-stimulated with cytokines for 11 days increased the MMP-mediated
aggrecan degradation, and not vice versa (data not shown). This confirm that our proteases has
been induced as expected 3 .
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