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Identification of important interactions between subchondral bone ...

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Contents<br />

Contents<br />

Abstract .......................................................................................................................................................... 7<br />

Sammendrag på dansk (abstract in Danish) ............................................................................................. 9<br />

CHAPTER 1<br />

Objectives .................................................................................................................................................... 11<br />

CHAPTER 2<br />

Introduction ................................................................................................................................................ 13<br />

2.1 Epidemiology and etiology <strong>of</strong> osteoarthritis ................................................................................ 13<br />

2.2 Biology <strong>of</strong> the joint .......................................................................................................................... 15<br />

2.2.1 Development <strong>of</strong> <strong>bone</strong> from a cartilage template ................................................................. 15<br />

2.2.2 Adult <strong>bone</strong> - macroscopic and microscopic organization .................................................. 17<br />

2.2.3 The cells <strong>of</strong> <strong>bone</strong> and their communications ....................................................................... 19<br />

2.2.4 Articular cartilage ...................................................................................................................... 22<br />

2.3 The pathology <strong>of</strong> Osteoarthritis .................................................................................................... 25<br />

2.3.1 A chondrocyte is not just a chondrocyte .............................................................................. 26<br />

2.3.2 The extracellular matrix <strong>of</strong> cartilage in OA .......................................................................... 28<br />

2.3.3 The <strong>subchondral</strong> <strong>bone</strong> in OA ................................................................................................. 29<br />

2.3.4 Diagnostics - biochemical markers as a tool ........................................................................ 30<br />

2.4 The effect <strong>of</strong> Glucocorticoids ........................................................................................................ 33<br />

2.5 References for CHAPTER 2 ......................................................................................................... 35<br />

CHAPTER 3<br />

Overview <strong>of</strong> OA models ........................................................................................................................... 43<br />

3.1 Pre-clinical models ........................................................................................................................... 43<br />

3.2 Advantages/disadvantages <strong>of</strong> pre-clinical models ...................................................................... 44<br />

3.2.1 In vitro .......................................................................................................................................... 44<br />

3.2.2 Ex vivo......................................................................................................................................... 44<br />

3.2.3 In vivo........................................................................................................................................... 46<br />

3.3 Ex vivo controls ................................................................................................................................ 47<br />

3.4 References for CHAPTER 3 ......................................................................................................... 48<br />

5

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