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 8: General discussion and conclusions<br />
aggrecanases. In contrast, MMPs primarily degrade low saturated aggrecan molecule. This<br />
suggests that it may be favourable to target aggrecanases in early OA and MMPs in later stages <strong>of</strong><br />
OA.<br />
We have also hypothesized that the endogenous proteases found in human OA<br />
depend on the stage <strong>of</strong> disease. This assumption is based on the fact that MMPs, and probably<br />
several other proteases, increase over time during the development <strong>of</strong> OA. However, the<br />
importance <strong>of</strong> cathepsins in this relation is unknown. Thus we used biochemical markers to<br />
assess the different endogenous proteases in normal vs. OA-cartilage. We found that CTX-II,<br />
NBC2 and AGNx-II are released in part by different proteolytic pathways in human OA<br />
cartilage. In addition, we suggest that the presence and role <strong>of</strong> endogenous proteases depend on<br />
the stage <strong>of</strong> OA (fig. 13). Further investigations on this topic may have significant value for<br />
development <strong>of</strong> new treatments for OA.<br />
Figure 13. Schematic illustration summarizing the four papers. The figure shows a femur head divided in a<br />
diseased and a normal half. The development <strong>of</strong> the whole femur head model is seen in PAPER I.<br />
Glucocorticoids (GC) decrease the degradation <strong>of</strong> damaged cartilage, but do not affect normal cartilage. GCs<br />
induce apoptosis in both normal and diseased <strong>bone</strong> (PAPER II). Aggrecan is divided in two different pools, with<br />
different molecular structures, which are degraded by different proteases (PAPER III). Proteases vary <strong>between</strong><br />
normal and OA cartilage. Furthermore, the presence and role <strong>of</strong> endogenous proteases probably depend on the<br />
stage <strong>of</strong> OA (PAPER IV). The figure was produced by Madsen, S.H.<br />
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