Identification of important interactions between subchondral bone ...

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CHAPTER 2: Introduction In healthy mature cartilage, the normal turnover of the ECM is kept in equilibrium by cytokines and growth factors, which stimulate the production of proteinases and matrix components. Chondrocytes maintain a low turnover rate with collagen having a half-life of more than 100 years and aggrecan having a half-life ranging from 3-24 years. In OA, the turnover is moved toward more degradation than formation of the cartilage 11,14 . Chondrocytes and osteoblasts both derive from the mesenchymal stem cells, suggesting a possible connection or natural communication between the cells. 24
2.3 The pathology of Osteoarthritis CHAPTER 2: Introduction OA is a complex disease of the entire joint. It is mainly characterized by the progressive degradation of articular cartilage, formation of osteophytes (bone outgrowths) and alterations and thickening of the subchondral bone (fig. 8) 60,61 . The main focus in the past decades has been on the articular cartilage as the affected tissue and biomechanics as the causative agent. The alterations in subchondral bone were believed to be secondary to the enforced inactivity. However, several studies have shown that normal cartilage turnover is dependent on a healthy subchondral bone 62,63 . Today, it is openly debated whether the pathogenesis of OA originates in the bone or in the cartilage compartment, and it is not clear to which extend these two compartments drives disease progression. An increased amount of evidence suggests a strong coupling between the subchondral bone and the articular cartilage turnover with pathological processes occurring concurrently in both compartments. Therefore, an optimal intervention strategy for OA likely includes the targeting of both bone and cartilage compartments that affects the pathophysiology of the whole joint by modulating and altering the interactions between the different cell types. Fig. 8. Illustration of a knee with severe osteoarthritis. A severe chronic osteoarthritic knee, with eroded cartilage, eroded meniscus, exposed bone and osteophytes (bone outgrowths). Adapted with few modifications 64 . 25
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: CHAPTER 2: Introduction Cartilage i
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 and 44: 139 Garnero P., Ayral X., Rousseau
Page 45 and 46: CHAPTER 3 Overview of OA models CHA
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
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still some controversy regarding th
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CHAPTER 6 CHAPTER 6: PAPER III PAPE
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Biomarkers Downloaded from informah
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CHAPTER 7 CHAPTER 7: PAPER IV PAPER
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Introduction CHAPTER 7: PAPER IV Ca
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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
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Appendix I 107
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Appendix I 109
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Appendix I 111
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Biochemical Markers of Joint Tissue
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