Osteoimmunology

Interactions of the Immune and Skeletal Systems

Joseph Lorenzo, Mark Horowitz, Yongwon Choi, Hiroshi Takayanagi, Georg Schett

• Publisher: Academic Press
• Year: 2015
• Edition: 2
• eBook ISBN:
  9780128006276
• Topic: Medicine
• Subtopic: Immunology

Osteoimmunology: Interactions of the Immune and Skeletal Systems, Second Edition, explores the advancements that have been made in the field during the last 40 years, including valuable information on our understanding of the interactions between hematopoietic, immune, and bone cells, now known as the field of osteoimmunology. This comprehensive work offers the most extensive summaries of research trends in the field and their translation into new therapeutics. Early chapters deal with the development of osteoblasts, osteoclasts, hematopoietic stem cells, T and B-lymphocytes, and communications between these cellular elements, while later sections contain discussions of the signaling pathways by which RANKL influences osteoclast development and function. Subsequent chapters explore the effects that estrogen has on bone and the immune system, the development of pathologic conditions, and the growing research around osteoporosis, Paget's disease, the genetics of bone disease, and bone cancer metastasis. - Explains the intricate interaction between the immune system and bone - Features detailed discussions of the key cellular and molecular mechanisms governing the homeostasis of the individual systems - Facilitates greater understanding of osteoimmunologic networks, their environments, and how this understanding leads to better treatments for human diseases involving both systems

Chapter 1

Overview: The Developing Field of Osteoimmunology

Joseph Lorenzo MD^*

Yongwon Choi PhD^**

Mark C. Horowitz PhD^†

Hiroshi Takayanagi PhD^‡

Georg Schett MD^§
* Department of Medicine and Orthopaedics, University of Connecticut Health Center, Farmington, CT, USA
^** Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
^† Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT, USA
^‡ Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO) Program, Takayanagi Osteonetwork Project, Tokyo, Japan
^§ Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany

Abstract

It has been over 40 years since the initial observations that cells of the immune system could influence the functions of bone cells. Since that time, significant strides have been made in our understanding of the interactions amonghematopoietic, immune, and bone cells, which is now known as the field of “osteoimmunology.”

In this introductory chapter, we will briefly establish some of the key features of osteoimmunology, which are described in greater detail in the subsequent chapters of this book and provide an overview of the changes in the first and second editions.

Keywords

bone

immune cells

osteoblasts

osteoclasts

It has been over 40 years since the initial observations that cells of the immune system influence the functions of bone cells. Since that time, significant strides have been made in our understanding of the interactions among hematopoietic, immune and bone cells, which is now known as the field of “osteoimmunology.”

This introductory chapter will establish briefly some of the key features of osteoimmunology, which are described in greater detail in the subsequent chapters of this book.

Bone cells originate from two lineages: osteoclasts and osteoblasts. Osteoclasts, which are responsible for bone resorption, are large, multinucleated cells that are uniquely capable of removing both the organic and mineral components of bone. Osteoclasts share a common origin with cells of the myeloid dendritic cell and macrophage lineages, and because of this respond to and produce many of the cytokines that regulate macrophage and dendritic cell function. The discovery of a tumor necrosis factor (TNF) family member, receptor activator of NFB ligand (RANKL), on activated T cells and its subsequent identification as one of the key differentiation and survival factors for osteoclasts, provided critical evidence for a potential link between normal immune responses and bone metabolism.

Bone is formed by osteoblasts that originate from mesenchymal stem cells (MSC). Osteoblast-lineage cells carry out at least three major functions: (1) they secrete bone matrix that mineralizes over time to form new bone; (2) they regulate osteoclast differentiation; (3) they support hematopoietic cell growth and differentiation. In addition some osteoblasts differentiate into osteocytes that are a specialized bone cell that senses mechanical force on bone and influences a variety of functions including osteoclast activity through the production of RANKL. It is now well accepted that MSC can differentiate into a variety of lineages including osteoblasts, adipocytes, muscle cells, and hematopoiesis-supporting stromal cells.¹ Osteoblast-lineage cells, which are sometimes referred to as stromal cells, produce a variety of cytokines that are critical for hematopoietic cell differentiation.

The first observation that immune cells could influence the activity of bone cells came from the finding that supernatants from phytohemagglutinin-stimulated peripheral blood monocytes of normal humans contained factors that stimulated bone resorption.² This activity was named osteoclast-activating factor (OAF). When it was eventually purified and sequenced, the principal stimulator of bone resorption in these crude OAF preparations was identified as the cytokine interleukin-1 (IL-1).³ In ad...

Table of contents

• Cover
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Foreword
• Preface
• Chapter 1: Overview: The Developing Field of Osteoimmunology
• Chapter 2: The Origins of the Osteoclast
• Chapter 3: Trafficking of Osteoclast Precursors
• Chapter 4: Osteoclast Biology: Regulation of Formation and Function
• Chapter 5: Osteoimmunology and the Osteoblast
• Chapter 6: The Variety of Osteocyte Function
• Chapter 7: Bone Marrow Hematopoietic Niches
• Chapter 8: RANK and RANKL of Bones, T Cells, and the Mammary Glands
• Chapter 9: The Effects of Immune Cell Products (Cytokines and Hematopoietic Cell Growth Factors) on Bone Cells
• Chapter 10: Coupling: The Influences of Immune and Bone Cells
• Chapter 11: The Role of the Immune System in the Development of Osteoporosis and Fracture Risk
• Chapter 12: The Role of Sex Steroids in the Effects of Immune System on Bone
• Chapter 13: The Role of the Immune System in the Local and Systemic Bone Loss of Inflammatory Arthritis
• Chapter 14: Osteoarthritis and the Immune System
• Chapter 15: Inflammatory Bowel Disease and Bone
• Chapter 16: The Role of the Immune System and Bone Cells in Acute and Chronic Osteomyelitis
• Chapter 17: The Role of the Immune System in Fracture Healing
• Chapter 18: The Role of the Immune System in the Effects of Cancer on Bone
• Chapter 19: Osteoimmunology in the Oral Cavity (Periodontal Disease, Lesions of Endodontic Origin, and Orthodontic Tooth Movement)
• Chapter 20: Marrow Adipose Tissue and its Interactions with the Skeletal, Hematopoietic, and Immune Systems
• Subject Index