Osteoimmunology (eBook)

Foreword 5
Contents 7
Contributors 9
Editor 9
Authors 9
The Role of Bone Marrow Edema and Lymphangiogenesisin Inflammatory-Erosive Arthritis 13
1 Introduction 13
2 Translational MRI Outcome Measures of Inflammatory-Erosive Arthritis Identify Bone Marrow Changes and Draining Lymph Node Function as Key Biomarkers of Disease Pathogenesis 14
3 Elucidating Bone Marrow Edema and Myelopoiesis in Murine Arthritis Using Contrast-Enhanced Magnetic Resonance Imaging 15
4 MR Imaging and Quantification of Draining Lymph Node Function in Inflammatory Arthritis 16
5 TNF Increases Bone Marrow Myelopoiesis by Increasing Proliferation Through Up-Regulation of c-Fms Expression on OCPs 17
6 TNF Inhibits Production of SDF-1 by Bone Marrow Stromal Cells and Increases Osteoclast Precursor Mobilization from Bone Marrow to Peripheral Blood 17
7 The Lymphatic Growth Factor, VEGF-C, is a RANKL Target Gene that Is Induced During Osteoclastogenesis and Contributes to Increased Lymphangiogenesis in Joints of Mice with Inflammatory-Erosive Arthritis 18
8 Conclusions 19
References 20
Activation of T Cells by Bisphosphonates 23
1 Bisphosphonates 23
2 Mechanism of Action of Bisphosphonates 24
3 T Cells and the Acute Phase Response to Nitrogen-Bisphosphonates 25
4 Triggering of the Acute-Phase Response to Nitrogen-Bisphosphonates In Vivo 27
5 Further Questions 29
6 Conclusion 29
References 30
Identification of Cell Cycle-Arrested Quiescent Osteoclast Precursors In Vivo 33
1 Introduction 34
2 Formation of Osteoclasts in BMP-2-Induced Ectopic Bone 35
3 Identification of QOPs as the Direct Osteoclast Precursors 35
4 Characteristics of QOP 37
5 In Vivo Identification of QOPs 38
6 Osteoclast Niche Prepared by Osteoblasts 40
References 41
Megakaryocyte-Bone Cell Interactions 43
1 Introduction 44
2 In Vivo Evidence: Mouse Models 44
2.1 TPO Overexpressing Mice 45
2.2 GATA-1 and NF-E2 Deficient Mice 46
2.3 Murine Model of Pt-vWD 47
3 MK-OC Interactions 48
4 MK-OB Interactions 49
5 Conclusion 50
References 50
Regulation of Osteoblast Differentiation by Runx2 54
1 Introduction 54
2 Expression of Runx2 and Osteoblast Markers During Bone Development 54
3 Osteoblast Differentiation at an Early Stage 55
4 Osteoblast Differentiation at a Late Stage 57
5 Regulation of Bone Matrix Protein Gene Expression by Runx2 59
References 59
Communication Between EphrinB2 and EphB4 Within the Osteoblast Lineage 61
1 Introduction Bone Remodeling 61
2 Communication from the Osteoblast to the Hemopoietic Lineage 62
3 Communication from Osteoclasts to the Osteoblasts in Order to Contribute to Bone Formation 62
4 How Do Cells of the Osteoblast Lineage Know How Much Bone to Make in a BMU? 64
5 Summary 68
References 68
The Unexpected Link Between Osteoclasts and the Immune System 71
1 Introduction 71
2 Transcriptional Machinery Activated by RANKL 73
3 Costimulatory Signals Along with RANK 73
4 Tec Family Kinases in B Cells and Osteoclasts 74
5 Cathepsin K in Dendritic Cells 74
6 Perspective 76
References 77
NFATc1 in Inflammatory and Musculoskeletal Conditions 79
1 Introduction 79
2 NFATc1 and Osteoclastogenesis 80
3 NFATc1 and Cherubism 81
4 NFATc1 and Hair Follicle Growth: Explaining an Untoward Side Effect of Calcineurin Inhibitors 82
5 Conclusions and Future Directions 82
References 82
Novel Functions of RANK(L) Signaling in the Immune System 86
1 RANK(L) Signaling in the Immune System 87
1.1 Lymph Node Development 87
1.2 Dendritic Cells 88
1.3 RANK(L) Signaling in the Thymus 91
1.4 Extramedullary Haematopoiesis and B Cell Phenotypes 92
2 RANKL-RANK Signaling Can Mediate UV-Induced Immunosuppression 93
3 T Cells and Bone Loss 94
4 RANKL-RANK as Key Triggers of Bone Loss in Rheumatoid Arthritis 95
5 RANKL Inhibition as a New Therapy to Control Bone Loss in Human Patients 98
6 Conclusions 99
References 99
Eph and Ephrin Interactions in Bone 104
1 Introduction 104
2 Ephrin-Eph Family 105
3 EphrinB2-EphB4 in Osteoclasts and Osteoblasts 105
3.1 Coupling Between Bone Resorption and Bone Formation 106
3.2 Osteoarthritis and Cancer Induced Bone Disease 107
3.3 Monocytes 107
3.4 Downstream Signaling of EphrinB2 and EphB4 108
4 Roles of Other Ephrin and Eph Family Members in Bone Cells 109
5 Future Directions 110
References 111
How Do Bone Cells Secrete Proteins? 113
References 117
Regulation of Osteoclast Apoptosis by Bcl-2 Family Protein Bim and Caspase-3 118
1 Introduction 118
2 Postranslational Regulation of Bim in MEF/Bcl-2 Cells 119
3 Bim Expression Is Downredulated by Caspase-3 in Osteoclasts 120
4 Caspase-3 Regulates Survival and Activation of Osteoclasts 120
5 Conclusion 121
References 122
Regulation of Bone Formation and Immune Cell Development by Schnurri Proteins 124
1 Introduction 124
2 Schnurri Protein Family 125
3 Regulation of Immune Cell Function by Schnurri Proteins 126
4 Schnurri Proteins and Skeletal Biology 127
5 Conclusions 128
References 128
Index 130