Identification of important interactions between subchondral bone ...

More documents

Recommendations

Info

CHAPTER 2: Introduction 18 Fig. 3. Schematic drawing of a long bone. A femur bone divided in sections: epiphyses, metaphyses, and a diaphysis. The different types of bone are shown; cortex (hard) and trabecular (spongy) bone. The proximal epiphysis (femur head) and the distal epiphysis are covered with cartilage to provide a smooth friction (during movement). The figure was produced by Madsen, S.H. The weight bearing bones, such as the femur and tibia that comprises the knee, have two opposite and important functions. The first is to resist loading, thus the bone must be stiff. The second is to be flexible to withstand shock, compression and tension by energy absorption and deformation 21 . The stiffness is achieved by mineralization and flexibility is achieved by a suitable organic matrix composition. However, if the bone matrix is too mineralized, it will become brittle and more prone to fractures, whereas if it is under-mineralized, the bone will be too flexible and will crack more readily. Therefore, the functionality of the bone highly depends on the ratio of organic and inorganic matrices 21 . In mammalian bone, the inorganic part of the matrix (50-70%) consist of hydroxyapatite crystals [3Ca 3(PO 4) 2·(OH) 2], which are layered on and within collagen fibres, ensuring bone matrix stiffness (mineralization). The crystals tend to orient in the same direction as the collagen fibres. The organic part of the matrix (20-40%) consists mainly of collagen type I (approximately 90%), but also glycoproteins, proteoglycans, and non-collagenous proteins. The collagen type I molecule is a triple helix (described further in section 2.3.4), which is assembled into fibres, providing the tensile strength of the matrix. The orientation of the collagen fibres determines the microscopic structure of the bone. During bone development or fracture healing, where bone is formed very rapidly, there is no preferential organization of the collagen fibres; this type of bone is called woven bone (fig. 4) 17 . Woven bone is characterized by irregular bundles of collagen fibres and calcification, which occur in irregularly distributed patches. Woven bone is progressively replaced by mature lamellar bone (fig. 4) during the remodelling process that
CHAPTER 2: Introduction follows normal development or healing. Lamellar bone is characterized by organized fibres, which are forming arches for optimal bone strength. The lamellae can be parallel to each other if deposited along a flat surface (trabecular bone) or concentric if deposited on a surface surrounding a channel centred on a blood vessel 17,22,23 . 2.2.3 The cells of bone and their communications 19 Fig. 4. Lamellar and woven bone. Histological cut from fibula of rabbit showing details of lamellar bone concentrically organized and woven bone mixed with cartilage and calcified cartilage tissues 24 . Bone contains several types of cells, which are important during development, repair, and maintenance. During bone development, the woven bone is modelled by resorption of calcified cartilage by osteoclasts and formation of bone by osteoblasts, independently of each other (not directly coupled) 16,25,26 . This is different in adult bone, where the tissue is constantly being remodelled by a communication/coupling between osteoclasts and osteoblasts, which enable bone to regenerate old or damaged tissue itself, adapt to changing stress environments, and control calcium homeostasis. Activation of the bone remodelling cycle is believed to be initiated by the osteocytes 15,21,27,28 , which comprises the most abundant cell type in bone. Osteocytes are cells trapped in the bone matrix. They rest in fluid-filled lacunae and communicate with surrounding cells via extensions called canaliculi 23,29 . When bone ages, the tissue eventually suffers microdamage and the surrounding osteocytes undergo apoptosis, which leads to signalling to the nearest bone lining cells (fig. 5A). This results in increased expression of receptor activator of nuclear factor kappa-B ligand (RANKL), which attracts osteoclast precursors to the damaged area and initiates osteoclastogenesis. Osteoclasts derived from hematopoietic stem cells that are differentiated into monocytes and subsequently pre-osteoclasts, which then fuse into large multinucleated osteoclasts. The two cytokines, macrophage colony stimulating factor (M-CSF) and RANKL, are produced by the cells of the osteoblast lineage, and are very important for the differentiation of the osteoclasts (fig. 5A).
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: CHAPTER 2: Introduction Also osteob
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 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
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 83 and 84:
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
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
Page 97 and 98:
CHAPTER 7: PAPER IV Detection of ke
Page 99 and 100:
CHAPTER 7: PAPER IV The MMP inhibit
Page 101 and 102:
CHAPTER 7: PAPER IV The pre-stimula
Page 103 and 104:
CHAPTER 8 CHAPTER 8: General discus
Page 105 and 106:
Future perspectives CHAPTER 8: Futu
Page 107 and 108:
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
show all

Identification of important interactions between subchondral bone ...

Create successful ePaper yourself

Delete template?

Save as template?