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