Immunology and bone

J Biochem. 2013 Jul;154(1):29-39. doi: 10.1093/jb/mvt049. Epub 2013 Jun 7.

Abstract

It is now well acknowledged that the immune and skeletal systems interact and affect one another during developmental physiology and pathology. With the aid of modern conditional gene targeting and transgenic technologies, this field of interdisciplinary research, known as osteoimmunology, is rapidly advancing. Numerous bone phenotypes have been described in immune-compromised gene-deficient mice and, albeit to a lesser extent, immune deficiencies exist in osteo-compromised gene-deficient mice, suggesting that bone cells themselves actually regulate the development of immune cells directly. In this review, I discuss the essential role of key cytokines, signalling transduction pathways and transcription factors during immune and bone development, and how pathology driven dysregulation of these shared mechanisms can lead to clinical manifestations. Diseases that are within the remit of osteoimmunology continue to cause significant morbidity, for example, rheumatoid arthritis, osteoporosis, multiple myeloma and breast/prostate cancer. The complexity and overlapping cellular and molecular interactions between the immune and bone tissues, mean that despite fervent research of these diseases, it remains a major challenge to discover therapeutics that can specifically target one system without detrimentally affecting the other.

Keywords: RANKL; T cell; haematopoietic stem cell; osteoblast; osteoclast.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Bone and Bones / immunology*
  • Bone and Bones / metabolism
  • Calcium Signaling
  • Female
  • Humans
  • Male
  • Mice
  • Models, Biological
  • NFATC Transcription Factors / immunology
  • NFATC Transcription Factors / metabolism
  • Osteoclasts / immunology
  • Osteoclasts / metabolism
  • Osteoprotegerin / genetics
  • Osteoprotegerin / immunology
  • Osteoprotegerin / metabolism
  • RANK Ligand / genetics
  • RANK Ligand / immunology
  • RANK Ligand / metabolism
  • Receptor Activator of Nuclear Factor-kappa B / genetics
  • Receptor Activator of Nuclear Factor-kappa B / immunology
  • Receptor Activator of Nuclear Factor-kappa B / metabolism
  • Signal Transduction
  • Stem Cell Niche / immunology
  • T-Lymphocyte Subsets / immunology

Substances

  • NFATC Transcription Factors
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B