Communication between the skeletal and immune systems

Abstract

In the last two decades, numerous researchers have focused on elucidating the relationship between the skeletal and immune systems with respect to their regulatory mechanisms. It has now become clear that osteoclasts are derived from the same myeloid precursor cells that can differentiate into macrophages and myeloid dendritic cells. In addition, bone and immune cells coexist in the common microenvironment of the bone marrow and are thus influenced by similar mediators. Discovery of a common regulatory mechanism via the receptor activator of nuclear factor kappa-B ligand (RANKL)–receptor activator of NF-κB (RANK)–osteoprotegerin (OPG) axis in both the bone and immune system has not only increased understanding of the fundamental processes of bone homeostasis but has further crystalized understanding of the definitive regulatory correlation between bone and immunity. Moreover, many of the soluble mediators produced by immune cells, including cytokines, chemokines, and growth factors, regulate the activities of osteoclasts and osteoblasts. This increased recognition of the complex interactions between the immune system and bone has led to the development of the interdisciplinary field of osteoimmunology. In this review, we summarize the characteristics of bone cells and the soluble mediators responsible for crosstalk between the skeletal and immune systems. A more complete appreciation of the interactions between immune and bone cells should lead to better therapeutic strategies for diseases that affect either or both systems.