Identification of important interactions between subchondral bone ...

CHAPTER 8: General discussion and conclusions
aggrecanases. In contrast, MMPs primarily degrade low saturated aggrecan molecule. This
suggests that it may be favourable to target aggrecanases in early OA and MMPs in later stages of
OA.
We have also hypothesized that the endogenous proteases found in human OA
depend on the stage of disease. This assumption is based on the fact that MMPs, and probably
several other proteases, increase over time during the development of OA. However, the
importance of cathepsins in this relation is unknown. Thus we used biochemical markers to
assess the different endogenous proteases in normal vs. OA-cartilage. We found that CTX-II,
NBC2 and AGNx-II are released in part by different proteolytic pathways in human OA
cartilage. In addition, we suggest that the presence and role of endogenous proteases depend on
the stage of OA (fig. 13). Further investigations on this topic may have significant value for
development of new treatments for OA.
Figure 13. Schematic illustration summarizing the four papers. The figure shows a femur head divided in a
diseased and a normal half. The development of the whole femur head model is seen in PAPER I.
Glucocorticoids (GC) decrease the degradation of damaged cartilage, but do not affect normal cartilage. GCs
induce apoptosis in both normal and diseased bone (PAPER II). Aggrecan is divided in two different pools, with
different molecular structures, which are degraded by different proteases (PAPER III). Proteases vary between
normal and OA cartilage. Furthermore, the presence and role of endogenous proteases probably depend on the
stage of OA (PAPER IV). The figure was produced by Madsen, S.H.
102