The immune system, bone and RANKL

•Bone and immune systems regulate each other and share many regulatory molecules.•RANKL is expressed on mesenchymal cells of the bone and activated T and B cells.•RANKL is responsible for bone loss in the arthritic joint.•RANKL has both pro- and anti-inflammatory effects in the immune system.•Osteoimmunology is an interdisciplinary field embracing bone and immune systems.

Bone and immune systems are tightly linked. In the past years, many molecules originally believed to belong to the immune system were found to function in bone cells. It is now evident that the two systems are coregulated by many shared cytokines and signaling molecules. Here we exemplify the complex interaction between bone metabolism and immune response focusing on the multifaceted role of receptor activator of NF-κB ligand (RANKL). RANKL is expressed by cells of both systems, is an essential regulator of bone degradation and exerts either pro or anti-inflammatory effects on the immune response. In the present review, we summarize the multiple functions of RANKL in bone and in the immune systems, aiming to provide an overview of the field of osteoimmunology.