Book review

Osteoimmunology: Interactions of the Immune and Skeletal Systems. Edited by Joseph Lorenzo, Yongwon Choi, Mark Horowitz, and Hiroshi Takayanagi. xiv + 478 pp. Boston, MA: Academic Press (Elsevier). 2011. $99.00 (cloth).

Miguel Angel García-pérez*, * Department of Genetics, School of Biology, Institute of Health Research Hospital Clinic of Valencia (INCLIVA), University of Valencia, Spain.

Until relatively recently, the bone was considered to be an organ whose study was “boring” because its functions of protection, support, and regulation of mineral homeostasis were not attractive enough to entice us to dedicate our time and effort to their study. In my opinion, however, this perception began to change in the 1970s with the description of factors secreted into the medium by cells of the immune system and upon activation, stimulated bone resorption. Since then numerous molecules and several types of immune system cells that influence the activity of bone cells have been described. But the opposite has also happened, that is, we have found bone cells involved in the differentiation of immune cells in the niche shared by both cell types. All this has contributed to the birth of osteoimmunology, a new branch of multidisciplinary biomedical research that has, among its objectives, the study and understanding of the close relationship between the immune system and the skeletal system and bone metabolism. And the name was coined in 2000 by Arron and Choi, the latter, one of the editors of this book (Arron and Choi, 2000).

The first several chapters of this book present us with an array of information and basic research (Chapters 1–9). Afterward, others describe the current knowledge of this discipline in a number of pathologies like inflammatory arthritis, acute and chronic osteomyelitis, hematologic malignancies, inflammatory bowel disease or periodontitis, among others (Chapters 10–15). Despite the inevitable overlaps, certain definitions in different chapters, the book is well written, with appropriate, but not excessive, graphic input. It represents the current state of the art for the topics and areas covered in the book.

In this review, I do not intend to summarize the different chapters of the book. Rather, I would like to highlight some of the newer concepts and those that I found better reflect the scope of this book, obligatory reading for those who study this discipline in the present or who are going to study it for years to come. Thus, for example, Galson and Roodman in Chapter 2 list morphological and biochemical characteristics of mature osteoclasts that suggest the existence of distinct subtypes of osteoclasts and show that under certain circumstances some cell types such as dendritic cells and B-cells can differentiate into osteoclasts. In Chapter 3, Hesslein et al. have written a review of the adaptive immune response in a clear and exhaustive manner that is welcome since it facilitates the understanding of certain concepts and processes that appear in different parts of the book. Henry and Kronenberg, in Chapter 4, expound on the novel concept that cells of osteoblast lineage support hematopoietic stem cells, note the importance of cellular microenvironment, and point out the implication of such main signaling pathways as the angiopoietin-1/Tie2 or the calcium-sensing receptor or Notch signaling, among others. Lian et al., in a really interesting Chapter 5, offer us a complete description of the differentiation pathways of osteoblasts and osteocytes, the hormonal regulation and regulatory networks that control osteoblast differentiation as different morphogens (bone morphogenic proteins (BMP)/transforming growth factor (TGFβ) and Wnt signaling) and mechanisms of transcriptional regulation (Hox genes, activator protein (AP)-1 factors, and Zn finger transcription factors). Finally, they describe the current and novel epigenetic functions of the role of Runx2 as a regulator of chromatin organization and of osteoblast differentiation by microRNAs. In Chapter 6, Faccio et al. provide much detail in the way they list the different factors and signaling pathways involved in the differentiation and activation of osteoclast as the pioneer of osteoimmunology. Interesting concepts presented in this chapter include the role of NFATc1, its auto-amplification, and epigenetic regulation in osteoclast differentiation. Lorenzo, in Chapter 7, elaborates a full description of all the cytokines and growth factors produced by immune system cells that affect bone metabolism. Martin et al., in Chapter 8, have reviewed not only cell communication in the bone multicellular unit and the influence of T- and B-cells on bone metabolism and regulation, but also a novel concept, the osteomacs as myeloid-macrophage cells which stimulate bone formation in vivo. The chapters dedicated to the different pathologies that occur with bone loss highlight the role of Th17 subset cells and regulatory T-cells (Treg) in the regulation of osteoclastogenesis and bone metabolism in rheumatoid arthritis, multiple myeloma and periodontitis (Chapters 10, 14, and 15), the defects in autophagy and its relationship with Crohn's disease (Chapter 11), and the new role of osteoblasts and osteoclasts in hematological stem cell mobilization, both in number and in function, in the defense against bone infection (Chapter 13).

Finally, the findings in this field of research will allow us to understand the cellular and molecular processes that lead to bone loss in a variety of situations and conditions like estrogen deficiency, rheumatoid arthritis, inflammatory bowel disease, periodontitis, and in tumors like multiple myeloma. In addition, presumably, this effort will also allow us identify key molecules that are specific to each condition which will allow us to develop therapeutic and pharmacological responses, an example of which is the development of the monoclonal antibody Denosumab (anti-RANKL), widely used clinically to treat different types of bone loss associated with osteoporosis, hormone suppression therapy, or bone metastases.

In summary, this book provides an updated and summarized review, basic, applied, and translational, to researchers and clinicians interested in the study of the mechanisms common to both bone biology and the immune system. Consequently, this text should be considered bedtime reading, a must for professionals (bone biologists, immunologists, oncologists, dentists, rheumatologists, endocrinologists, and of course, their fellow osteoimmunologists) since it is the state of the art for this exciting new discipline whose importance and relevance continues to grow exponentially in today's scientific literature.