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Identification of important interactions between subchondral bone ...

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CHAPTER 2: Introduction<br />

20<br />

Fig. 5. The remodelling cycle on trabecular<br />

<strong>bone</strong>. A) A microcrack or old <strong>bone</strong> causes<br />

osteocytic apoptosis, which induces RANKL<br />

expression by <strong>bone</strong> lining cells. This attracts<br />

monocytes to the damaged <strong>bone</strong> area, and<br />

osteoclastogenesis starts. The osteoclasts will<br />

start to resorb <strong>bone</strong>, which is followed by<br />

formation <strong>of</strong> new <strong>bone</strong> matrix by the osteoblasts.<br />

Osteoblasts that are trapped in the remodelled<br />

matrix become osteocytes, whereas the rest<br />

either die or become flattened osteoblast lining<br />

cells. B) The resorbing osteoclast seals tightly to<br />

the <strong>bone</strong> surface to create a closed local<br />

environment known as the resorption lacuna.<br />

This is where the <strong>bone</strong> resorption takes place, by<br />

lowering the pH (secretion <strong>of</strong> H + ) and by<br />

releasing proteases by exocytosis. The figures<br />

were produced by Madsen, S.H.<br />

Active osteoclasts can be characterized by their ruffled cell borders, which seal and degrade the<br />

underlying <strong>bone</strong> in the resorption pit, through the release <strong>of</strong> hydrogen ions (lowering <strong>of</strong> pH) and<br />

proteases (such as cathepsin K and matrix metalloproteases). The resorbed <strong>bone</strong> tissue is<br />

transported across the osteoclast in small vesicles and is released into the extracellular fluid (fig.<br />

5B.) 21 .

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