Osteoimmunology

Abstract

Osteoimmunology is an interdisciplinary research field combining the exciting fields of osteology and immunology. An observation that contributed enormously to the emergence of osteoimmunology was the accelerated bone loss caused by inflammatory diseases such as rheumatoid arthritis. Receptor activator of nuclear factor kappaB ligand (RANKL), which is the main regulator of osteoclastogenesis, was found to be the primary culprit responsible for the enhanced activation of osteoclasts: activated T cells directly and indirectly increased the expression of RANKL, and thereby promoted osteoclastic activity. Excessive bone loss is not only present in inflammatory diseases but also in autoimmune diseases and cancer. Furthermore, there is accumulating evidence that the very prevalent skeletal disorder osteoporosis is associated with alterations in the immune system. Meanwhile, numerous connections have been discovered in osteoimmunology beyond merely the actions of RANKL. These include the importance of osteoblasts in the maintenance of the hematopoietic stem cell niche and in lymphocyte development as well as the functions of immune cells participating in osteoblast and osteoclast development. Furthermore, research is being done investigating cytokines, chemokines, transcription factors and co-stimulatory molecules which are shared by both systems. Research in osteoimmunology promises the discovery of new strategies and the development of innovative therapeutics to cure or alleviate bone loss in inflammatory and autoimmune diseases as well as in osteoporosis. This review gives an introduction to bone remodeling and the cells governing that process and summarizes the most recent discoveries in the interdisciplinary field of osteoimmunology. Furthermore, an alternative large animal model will be discussed and the pathophysiological alterations of the immune system in osteoporosis will be highlighted.