Osteoimmunology

Osteoimmunology (όστέον, osteon from Greek, “bone”; immunitas from Latin, “immunity”; and λόγος, logos, from Greek “knowledge”) is the study of the interface between the skeletal system and the immune system, comprising the “osteo-immune system”. It is also the study of shared components and mechanisms between the two systems in vertebrates, including ligands, receptors, signaling molecules and transcription factors. Some medical conditions in which this field is particularly relevant are bone metastases, rheumatoid arthritis, osteoporosis, osteopetrosis, and periodontitis. Studies in osteoimmunology reveal relationships between molecular communication among blood cells and structural pathologies in the body.

System similarities
The RANKL-RANK-OPG(osteoprotegerin) axis is an example of an important signaling system functioning both in bone and immune cell communication. RANKL is expressed on osteoblasts and activated T cells, whereas RANK is expressed on osteoclasts, and dendritic cells (DCs), both of which can be derived from myeloid progenitor cells. Surface RANKL on osteoblasts as well as secreted RANKL provide necessary signals for osteoclast precursors to differentiate into osteoclasts. RANKL expression on activated T cells leads to DC activation through binding to RANK expressed on DCs. OPG, produced by DCs, is a soluble decoy receptor for RANKL that competitively inhibits RANKL binding to RANK.

Crosstalk
The bone marrow cavity is important for the proper development of the immune system, and houses important stem cells for maintenance of the immune system. Within this space, as well as outside of it, cytokines produced by immune cells also have important effects on regulating bone homeostasis. Some important cytokines that are produced by the immune system, including RANKL, M-CSF, TNFa, ILs, and IFNs, affect the differentiation and activity of osteoclasts and bone resorption. During chronic inflammation, the balance of bone modeling and remodeling can be greatly affected, contributing to painful and/or visible disorders in bone metabolism.