Osteoimmunology - Interactions of the Immune and Skeletal Systems

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Osteoimmunology:Interactions of the Immuneand Skeletal Systems

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Contents

Contributors

Foreword

Preface

Chapter 1 Overview: The Developing Field of Osteoimmunology

References

Chapter 2 Origins of Osteoclasts

Introduction: osteoclasts

Hematopoietic origins of osteoclasts – insights from osteopetrosis

Generation of osteoclasts

More than one type of osteoclast?

Other OCL precursors

Conclusion

References

Chapter 3 The Adaptive Immune Response

Introduction

T-cell development and function

B-cell development and function

Acknowledgments

References

Chapter 4 The Role of Bone Cells in Establishing the Hematopoietic Stem Cell Niche

Introduction

The osteoblast lineage is heterogeneous

Cells of the osteoblast lineage support hematopoietic stem cells

Signaling pathways implicated in osteoblast–HSC communication

Other signaling pathways in the microenvironment that may involve osteoblasts

Osteoblasts and their precursors also support other hematopoietic lineages

Other components of the hematopoietic niche

The microenvironment and disease

The bone marrow HSC microenvironment is complex

References

Chapter 5 Osteoblasts and their Signaling Pathways: New Frontiers for Linkage to the Immune System

Introduction

Bone as a connective tissue, organ and supportive environment for other tissues

Functional activities of osteoblast lineage cells

Regulatory networks controlling the progression of osteoblast differentiation

Osteoblast and immune cell crosstalk: A peek into the future

Immune responses and bone pathology: Effects of inflammation on bone in rheumatoid arthritis

Acknowledgments

References

Chapter 6 The Osteoclast: The Pioneer of Osteoimmunology

Introduction

RANKL and RANK, an osteoclastogenic cytokine and its receptor

TRAF6: the multifunctional signaling molecule activated by RANK

What happens downstream of TRAF6?

The role of NF-?B in osteoclast differentiation

The critical role of AP-1 transcription factors

MAPKs activated by RANKL

NFATc1 is a master transcription factor of osteoclast differentiation

Autoamplification of NFATc1 and its epigenetic regulation

Transcriptional control governed by NFATc1

Co-stimulatory receptors for RANK signal: FcR? and DAP12

Importance of ITAM co-stimulatory signals in humans: Nasu-Hakola disease

Additional co-stimulatory signals involved in osteoclastogenesis

Receptors signaling through DAP12

Src family kinases: activation of ITAM signaling

Syk kinase: downstream of DAP12/FcR??

PLC?2: enzyme and adaptor molecule

Tec kinases: integrating RANK and ITAM signaling

Negative regulatory role of DAP12

M-CSF and c-Fms: a road to proliferation and survival

M-CSF signaling

Erk and PI3K signaling

The osteoclasttnqh_x2019s job: bone resorption

Osteoclast cytoskeleton: the podosomes and the sealing zone

Osteoclast cytoskeleton: the microtubules and the sealing zone

Osteoclast functional structure: the ruffled border

Osteoclast and bone matrix: role of ?v?3 integrin

Integrin-associated proteins

M-CSF and the osteoclast cytoskeleton

Conclusion

References

Chapter 7 The Effects of Immune Cell Products (Cytokines and Hematopoietic Cell Growth Factors) on Bone Cells

Receptor activator of nuclear factor-kB ligand(RANKL), receptor activator of nuclear factor-kB(RANK), and osteoprotegerin (OPG)

Macrophage colony-stimulating factor

Additional colony-stimulating factors

Interleukin-1

Tumor necrosis factor

Additional TNF superfamily members

Interleukin-6

Additional interleukin-6 family members

Interleukin-7

Interleukin-8 and other chemokines

Interleukin-10

Interleukin-12

Interleukin-15

Interleukin-17, interleukin-23, and interleukin-27

Interleukin-18

Interferons

Additional cytokines

References

Chapter 8 Interactions Among Osteoblasts, Osteoclasts, and Other Cells in Bone

Introduction

Osteoblasts, lining cells, and osteocytes

Bone modeling and remodeling

Cell communication within the bone multicellular unit

Cell communication from beyond the bone multicellular unit

Summary and conclusions – remodeling and the coupling of bone formation to resorption

Acknowledgments

References

Chapter 9 The Role of the Immune System in the Development of Osteoporosis

Introduction

Patterns of age-related bone loss and fractures

Relationship between sex steroid production and bone loss

Sex steroid regulation of bone remodeling

Estrogen and the immune system

Potential effects of estrogen deficiency on general immunity

Effects of aging on bone loss independent of changes in sex steroid production

Secondary causes of osteoporosis mediated by the immune system

Prospects for treatment of osteoporosis by regulation of immune cytokines

Summary and conclusions

Acknowledgments

References

Chapter 10 The Role of the Immune System in the Bone Loss of Inflammatory Arthritis

Introduction

Bone disease associated with RA

Joint margin and subchondral bone loss in RA

Peri-articular bone loss

Generalized bone loss

Seronegative spondyloarthropathies

Acknowledgment

References

Chapter 11 Inflammatory Bowel Disease and Bone

Introduction

The intestinal immune system

Innate immune functions and IBD pathogenesis

The adaptive immune system and IBD

Immunological differences between Crohn's disease and ulcerative colitis

IBD and osteoimmunology

Effects of IBD on bone mass

Mechanisms by which IBD affects bone mass

Conclusion

References

Chapter 12 The Role of the Immune System in Fracture Healing

Bone repair as a postnatal regenerative process

Fracture healing cascade

Role of mesenchymal stem cells in the modulation of immune function

Cytokines involved in fracture healing

Phase-specific roles of cytokines in fracture healing

Role of non-steroidal anti-inflammatory drugs in fracture healing

References

Chapter 13 The Role of the Immune System and Bone Cells in Acute and Chronic Osteomyelitis

Introduction

Mechanism of microbial infection in the pathogenesis of osteomyelitis

The host response to osteomyelitis

Osteoblasts: the last line of defense and a novel substrate for bone infections

Osteoclasts modulate immune responses and functions of various cells during infections in bone

Osteoclasts and osteoclast precursors affect osteoblast functions

Osteoclasts as regulators of hematopoietic stem cell functions

The role of dendritic cells and cellular immunity in bone infection

DCs in adaptive immunity and infection

DCs in innate immunity and infection

DCs and osteoclasts in infection

The role of B cells in bone infection and the potential of passive immunization

References

Chapter 14 The Role of the Immune System in Hematologic Malignancies that Affect Bone

Introduction

Innate immunity – macrophages, dendritic cells, and natural killer cells

Adaptive immunity

Hedgehog signaling

TNF receptor superfamily and NF-?B

Therapeutic approaches and effects on immune cells

Conclusions

References

Chapter 15 Osteoimmunology in the Oral Cavity (Periodontal Disease, Lesions of Endodontic Origin and Orthodontic Tooth Movement)

Introduction

Periodontal diseases

Lesions of endodontic origin

Orthodontic tooth movement

Conclusions

Acknowledgments

References

Index

Color Plates