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Identification of important interactions between subchondral bone ...

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CHAPTER 3: Overview <strong>of</strong> OA models<br />

<strong>of</strong> OA 7,18 . The biochemical markers can be used in combination with histology/<br />

immunohistochemistry to further characterize the pathogenesis <strong>of</strong> the cartilage 14 . The articular<br />

cartilage explants model has been used in PAPER II, III, and IV to evaluate ECM turnover and<br />

enzymatic activity.<br />

There is an urgent need for the discovery and development <strong>of</strong> new treatments for<br />

OA. A fundamental step in discovering new therapies for OA is to critically evaluate our<br />

understanding <strong>of</strong> the etiology <strong>of</strong> the disease, including the complex relationship <strong>between</strong> cartilage<br />

and <strong>bone</strong>. Thus, the cartilage explants model is not complete as it only comprises cartilage. When<br />

the present PhD-project was initiated there were neither biological models nor tools that allowed<br />

the investigation <strong>of</strong> the interaction <strong>between</strong> the <strong>bone</strong> and cartilage cells. Thus, there was a strong<br />

need for an ex vivo model system comprising both <strong>bone</strong> and cartilage, which could provide a<br />

unique opportunity to investigate cell-cell <strong>interactions</strong> and test novel drug candidates for OA.<br />

This resulted in testing murine femur heads as potential candidates to constitute a novel explants<br />

model since the femur heads comprise both <strong>bone</strong> and cartilage (fig. 12). Importantly, the femur<br />

head is a closed system, which would not be damaged during isolation procedures (except on the<br />

shaft), keeping the homogeneity high <strong>between</strong> the samples, whereas the cartilage explants have a<br />

low homogeneity <strong>between</strong> the samples (Table 1). Isolation as a whole unit reduces the stress on<br />

the cells as the ECM is still intact and uncontrollable repair mechanisms are avoided.<br />

Fig. 12. The femur head comprises both <strong>bone</strong> and cartilage. The femur head is isolated from the femur<br />

by cutting with a scissor. The femur head is a whole unit, which is only damaged at the cutting site (at the<br />

femur neck). The femur head comprises both <strong>bone</strong> and cartilage, but also the transition zone <strong>of</strong><br />

<strong>bone</strong>/cartilage (e.g. growth plate during development). The <strong>interactions</strong> <strong>between</strong> the cells from the different<br />

compartments, primarily the chondrocytes, osteoclasts, and osteoblasts, can be investigated in this femur<br />

head explants model. The figure was produced by Madsen, S.H.<br />

The pathology <strong>of</strong> OA involves the whole joint. The<br />

development <strong>of</strong> a novel ex vivo model comprising both<br />

<strong>bone</strong> and cartilage is characterized in PAPER I<br />

45

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