Osteoimmunology (eBook)

Front Cover 1
Osteoimmunology:Interactions of the Immuneand Skeletal Systems 4
Copyright 5
Contents 6
Contributors 8
Foreword 12
Preface 14
Chapter 1 Overview: The Developing Field of Osteoimmunology 16
References 19
Chapter 2 Origins of Osteoclasts 22
Introduction: osteoclasts 23
Hematopoietic origins of osteoclasts – insights from osteopetrosis 26
Generation of osteoclasts 32
More than one type of osteoclast? 43
Other OCL precursors 47
Conclusion 49
References 49
Chapter 3 The Adaptive Immune Response 58
Introduction 58
T-cell development and function 59
B-cell development and function 73
Acknowledgments 87
References 87
Chapter 4 The Role of Bone Cells in Establishing the Hematopoietic Stem Cell Niche 96
Introduction 96
The osteoblast lineage is heterogeneous 97
Cells of the osteoblast lineage support hematopoietic stem cells 98
Signaling pathways implicated in osteoblast–HSC communication 101
Other signaling pathways in the microenvironment that may involve osteoblasts 103
Osteoblasts and their precursors also support other hematopoietic lineages 105
Other components of the hematopoietic niche 106
The microenvironment and disease 108
The bone marrow HSC microenvironment is complex 108
References 109
Chapter 5 Osteoblasts and their Signaling Pathways: New Frontiers for Linkage to the Immune System 116
Introduction 117
Bone as a connective tissue, organ and supportive environment for other tissues 118
Functional activities of osteoblast lineage cells 123
Regulatory networks controlling the progression of osteoblast differentiation 128
Osteoblast and immune cell crosstalk: A peek into the future 139
Immune responses and bone pathology: Effects of inflammation on bone in rheumatoid arthritis 140
Acknowledgments 143
References 143
Chapter 6 The Osteoclast: The Pioneer of Osteoimmunology 156
Introduction 157
RANKL and RANK, an osteoclastogenic cytokine and its receptor 158
TRAF6: the multifunctional signaling molecule activated by RANK 159
What happens downstream of TRAF6? 161
The role of NF-?B in osteoclast differentiation 162
The critical role of AP-1 transcription factors 163
MAPKs activated by RANKL 164
NFATc1 is a master transcription factor of osteoclast differentiation 164
Autoamplification of NFATc1 and its epigenetic regulation 166
Transcriptional control governed by NFATc1 167
Co-stimulatory receptors for RANK signal: FcR? and DAP12 167
Importance of ITAM co-stimulatory signals in humans: Nasu-Hakola disease 171
Additional co-stimulatory signals involved in osteoclastogenesis 172
Receptors signaling through DAP12 172
Src family kinases: activation of ITAM signaling 173
Syk kinase: downstream of DAP12/FcR?? 174
PLC?2: enzyme and adaptor molecule 174
Tec kinases: integrating RANK and ITAM signaling 175
Negative regulatory role of DAP12 176
M-CSF and c-Fms: a road to proliferation and survival 177
M-CSF signaling 177
Erk and PI3K signaling 178
The osteoclasttnqh_x2019s job: bone resorption 179
Osteoclast cytoskeleton: the podosomes and the sealing zone 180
Osteoclast cytoskeleton: the microtubules and the sealing zone 180
Osteoclast functional structure: the ruffled border 181
Osteoclast and bone matrix: role of ?v?3 integrin 183
Integrin-associated proteins 186
M-CSF and the osteoclast cytoskeleton 189
Conclusion 190
References 190
Chapter 7 The Effects of Immune Cell Products (Cytokines and Hematopoietic Cell Growth Factors) on Bone Cells 202
Receptor activator of nuclear factor-kB ligand(RANKL), receptor activator of nuclear factor-kB(RANK), and osteoprotegerin (OPG) 203
Macrophage colony-stimulating factor 204
Additional colony-stimulating factors 205
Interleukin-1 206
Tumor necrosis factor 207
Additional TNF superfamily members 208
Interleukin-6 209
Additional interleukin-6 family members 210
Interleukin-7 211
Interleukin-8 and other chemokines 212
Interleukin-10 215
Interleukin-12 215
Interleukin-15 216
Interleukin-17, interleukin-23, and interleukin-27 216
Interleukin-18 217
Interferons 217
Additional cytokines 218
References 219
Chapter 8 Interactions Among Osteoblasts, Osteoclasts, and Other Cells in Bone 242
Introduction 243
Osteoblasts, lining cells, and osteocytes 243
Bone modeling and remodeling 253
Cell communication within the bone multicellular unit 255
Cell communication from beyond the bone multicellular unit 263
Summary and conclusions – remodeling and the coupling of bone formation to resorption 269
Acknowledgments 270
References 270
Chapter 9 The Role of the Immune System in the Development of Osteoporosis 284
Introduction 285
Patterns of age-related bone loss and fractures 285
Relationship between sex steroid production and bone loss 289
Sex steroid regulation of bone remodeling 291
Estrogen and the immune system 294
Potential effects of estrogen deficiency on general immunity 301
Effects of aging on bone loss independent of changes in sex steroid production 303
Secondary causes of osteoporosis mediated by the immune system 304
Prospects for treatment of osteoporosis by regulation of immune cytokines 305
Summary and conclusions 306
Acknowledgments 306
References 307
Chapter 10 The Role of the Immune System in the Bone Loss of Inflammatory Arthritis 316
Introduction 316
Bone disease associated with RA 317
Joint margin and subchondral bone loss in RA 318
Peri-articular bone loss 326
Generalized bone loss 327
Seronegative spondyloarthropathies 330
Acknowledgment 334
References 334
Chapter 11 Inflammatory Bowel Disease and Bone 340
Introduction 340
The intestinal immune system 341
Innate immune functions and IBD pathogenesis 342
The adaptive immune system and IBD 343
Immunological differences between Crohn's disease and ulcerative colitis 344
IBD and osteoimmunology 345
Effects of IBD on bone mass 345
Mechanisms by which IBD affects bone mass 346
Conclusion 350
References 350
Chapter 12 The Role of the Immune System in Fracture Healing 358
Bone repair as a postnatal regenerative process 359
Fracture healing cascade 361
Role of mesenchymal stem cells in the modulation of immune function 365
Cytokines involved in fracture healing 366
Phase-specific roles of cytokines in fracture healing 369
Role of non-steroidal anti-inflammatory drugs in fracture healing 373
References 376
Chapter 13 The Role of the Immune System and Bone Cells in Acute and Chronic Osteomyelitis 384
Introduction 384
Mechanism of microbial infection in the pathogenesis of osteomyelitis 385
The host response to osteomyelitis 387
Osteoblasts: the last line of defense and a novel substrate for bone infections 389
Osteoclasts modulate immune responses and functions of various cells during infections in bone 390
Osteoclasts and osteoclast precursors affect osteoblast functions 393
Osteoclasts as regulators of hematopoietic stem cell functions 394
The role of dendritic cells and cellular immunity in bone infection 395
DCs in adaptive immunity and infection 395
DCs in innate immunity and infection 396
DCs and osteoclasts in infection 397
The role of B cells in bone infection and the potential of passive immunization 398
References 399
Chapter 14 The Role of the Immune System in Hematologic Malignancies that Affect Bone 406
Introduction 406
Innate immunity – macrophages, dendritic cells, and natural killer cells 407
Adaptive immunity 412
Hedgehog signaling 413
TNF receptor superfamily and NF-?B 413
Therapeutic approaches and effects on immune cells 415
Conclusions 418
References 419
Chapter 15 Osteoimmunology in the Oral Cavity (Periodontal Disease, Lesions of Endodontic Origin and Orthodontic Tooth Movement) 426
Introduction 427
Periodontal diseases 427
Lesions of endodontic origin 439
Orthodontic tooth movement 444
Conclusions 447
Acknowledgments 448
References 448
Index 458
Color Plates 470