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Suzi Høgh Madsen, PhD thesis 42
CHAPTER 3 Overview of OA models CHAPTER 3: Overview of OA models This Overview aims to introduce some of the different pre-clinical models used today to investigate the pathogenesis of OA with emphasis on the ex vivo model. In brief, the complexity and advantages/disadvantages of the different models and the motivation for developing the femur head model (PAPER I) are described. Further, the controls used in previous ex vivo models are evaluated in order to understand the selection of these controls for the present femur head model (PAPER I). 3.1 Pre-clinical models Clinical studies of OA in humans are expensive and very time consuming. Furthermore, clinical studies do not provide information about processes and mechanisms involved in pathogenic OA- tissues, which could be key information to prevent or stop the ongoing development of the disease. For these and ethical reasons, pre-clinical models are commonly used to investigate the metabolism of healthy/diseased bone or cartilage, which can be classified according to their complexity (fig. 11): In vitro; monolayer or pellet systems of isolated cells Ex vivo explants cultures, in which the cells are held in their natural matrix In vivo animal models; such as spontaneous, surgically induced, or transgenic, which resemble the human disease (apart from the species/origin) Each of these models has advantages and disadvantages depending on the purpose of the investigation. In the following section, the methodology behind the three models will be described in brief in relation to OA with main focus on the ex vivo model. Fig. 11. The different types of pre-clinical models. In an in vitro model, cells are isolated from their natural environments, which may cause them to change phenotype during culture. In an ex vivo model, the cells are maintained in their natural environments, but lack systemic influence (pressure, blood supply etc.). In in vivo models, the cells are maintained in their natural environment and host. The figure was produced by Madsen, S.H. 43
Page 1 and 2: F A C U L T Y O F S C I E N C E U N
Page 3 and 4: Supervisors University of Copenhage
Page 5 and 6: Preface Preface The work presented
Page 7 and 8: Contents Contents Abstract ........
Page 9 and 10: Abstract Abstract Osteoarthritis (O
Page 11 and 12: Sammendrag på dansk Sammendrag på
Page 13 and 14: CHAPTER 1 Objectives CHAPTER 1: Obj
Page 15 and 16: CHAPTER 2 Introduction CHAPTER 2: I
Page 17 and 18: 2.2 Biology of the joint CHAPTER 2:
Page 19 and 20: CHAPTER 2: Introduction Also osteob
Page 21 and 22: CHAPTER 2: Introduction follows nor
Page 23 and 24: CHAPTER 2: Introduction When the jo
Page 25 and 26: CHAPTER 2: Introduction Cartilage i
Page 27 and 28: 2.3 The pathology of Osteoarthritis
Page 29 and 30: CHAPTER 2: Introduction number of a
Page 31 and 32: CHAPTER 2: Introduction Cysteine pr
Page 33 and 34: CHAPTER 2: Introduction include car
Page 35 and 36: 2.4 The effect of Glucocorticoids C
Page 37 and 38: 2.5 References for CHAPTER 2 1 WebM
Page 39 and 40: 51 Lorenz H. and Richter W. Osteoar
Page 41 and 42: 97 Nakamura H., Tanaka M., Masuko-H
Page 43: 139 Garnero P., Ayral X., Rousseau
Page 47 and 48: CHAPTER 3: Overview of OA models of
Page 49 and 50: 3.3 Ex vivo controls CHAPTER 3: Ove
Page 51 and 52: 19 Brandt K.D. Animal models of ost
Page 53 and 54: CHAPTER 4 CHAPTER 4: PAPER I PAPER
Page 55 and 56: 266 Cartilage 2(3) therapy for oste
Page 57 and 58: 268 Cartilage 2(3) Figure 1. Charac
Page 59 and 60: 270 Cartilage 2(3) Figure 4. The ca
Page 61 and 62: 272 Cartilage 2(3) Figure 5. Cytoki
Page 63 and 64: 274 Cartilage 2(3) Figure 6. The an
Page 65 and 66: 276 Cartilage 2(3) supports the inc
Page 67 and 68: 278 Cartilage 2(3) release and rece
Page 69 and 70: CHAPTER 5 CHAPTER 5: PAPER II PAPER
Page 71 and 72: leading to fragility fractures [12]
Page 73 and 74: after 1 week (Fig. 2F). The additio
Page 75 and 76: use a range of assays ranging from
Page 77 and 78: still some controversy regarding th
Page 79 and 80: CHAPTER 6 CHAPTER 6: PAPER III PAPE
Page 81 and 82: Biomarkers Downloaded from informah
Page 91 and 92: CHAPTER 7 CHAPTER 7: PAPER IV PAPER
Page 93 and 94: Introduction CHAPTER 7: PAPER IV Ca
Page 95 and 96:
Bovine articular cartilage experime
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CHAPTER 7: PAPER IV Detection of ke
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CHAPTER 7: PAPER IV The MMP inhibit
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CHAPTER 7: PAPER IV The pre-stimula
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CHAPTER 8 CHAPTER 8: General discus
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Future perspectives CHAPTER 8: Futu
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Appendix I Co-author declarations f
Page 109 and 110:
Appendix I 107
Page 111 and 112:
Appendix I 109
Page 113 and 114:
Appendix I 111
Page 115:
Biochemical Markers of Joint Tissue
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