Identification of important interactions between subchondral bone turnover and cartilage degradation in the pathogenesis of osteoarthritis

......................................................................................................................................................... 7 Sammendrag på dansk (abstract in Danish) ............................................................................................. 9 CHAPTER 1 Objectives .................................................................................................................................................... 11 CHAPTER 2 Introduction ................................................................................................................................................ 13 2.1 Epidemiology and etiology of osteoarthritis ................................................................................ 13 2.2 Biology of the joint .......................................................................................................................... 15 2.2.1 Development of bone from a cartilage template ................................................................. 15 2.2.2 Adult bone macroscopic and microscopic organization .................................................. 17 2.2.3 The cells of bone and their communications ....................................................................... 19 2.2.4 Articular cartilage ...................................................................................................................... 22 2.3 The pathology of Osteoarthritis .................................................................................................... 25 2.3.1 A chondrocyte is not just a chondrocyte .............................................................................. 26 2.3.2 The extracellular matrix of cartilage in OA .......................................................................... 28 2.3.3 The subchondral bone in OA ................................................................................................. 29 2.3.4 Diagnostics biochemical markers as a tool ........................................................................ 30 2.4 The effect of Glucocorticoids ........................................................................................................ 33 2.5 References for CHAPTER 2 ......................................................................................................... 35 CHAPTER 3 Overview of OA models ........................................................................................................................... 43 3.1 Pre-clinical models ........................................................................................................................... 43 3.2 Advantages/disadvantages of pre-clinical models ...................................................................... 44 3.2.1 In vitro .......................................................................................................................................... 44 3.2.2 Ex vivo......................................................................................................................................... 44 3.2.3 In vivo........................................................................................................................................... 46 3.3 Ex vivo controls ................................................................................................................................ 47 3.4 References for CHAPTER 3 ......................................................................................................... 48