The unexpected links between bone and the immune system

B one is a tissue of central importance, maintaining several relationships with other organs. Among these, the immune system, with which it shares molecular pathways, transcription factors, and several cytokines responsible for bone and immune cell regulation. A paradigm of this crosstalk comes from the studies of Hiroshi Takayanagi on the mechanisms underlying the development of rheumatoid arthritis, demonstrating the central role of a subset of T lymphocytes in the induction of exaggerated osteoclast activity, thus leading to erosion in the affected joints. RANKL/RANK (receptor activator of nuclear factor–kappaB [ligand]) is an important pathway shared by bone and the immune system. This pathway is essential for both osteoclastogenesis and lymphocyte differentiation, so that diseases due to inactivating mutations of RANKL or RANK, such as osteopetrosis, result in immunological defects in addition to altered bone phenotype. This study focuses on the description of the principal molecules/pathways shared with the immune system, which under both physiological and pathological conditions, regulate bone remodeling by acting on osteoclast formation and activity. We propose that the evidence available today strongly points to the osteoclast as a cell with immunological properties, in addition to its role in bone resorption.