Osteoimmunology: the effect of inflammation on bone

抄録

The bony skeleton enables locomotive activity, the storage of calcium, and the harboring of the hematopoietic stem cells from which blood and immune cells are derived. Although bone appears to be metabolically inert, it is actually a dynamic organ, under the active control of osteoblasts and osteoclasts. Excessive activity of osteoclasts leads to pathological bone resorption, as seen in a variety of local or generalized osteopenic conditions. Therefore, the elucidation of the regulatory mechanisms involved in osteoclastogenesis is critical for the understanding of the skeletal system in both health and disease. The immune and skeletal systems share various molecules, including cytokines, signaling molecules, transcription factors and membrane receptors. Investigation of rheumatoid arthritis (RA), as well as the cloning of RANKL and identification of the various bone phenotypes found in immune-compromised genetically modified mice, have highlighted the importance of the dynamic interplay between the two systems. RANKL stimulates osteoclastogenesis through nuclear factor of activated T cells (NFAT) c1, which is also a crucial regulator of immunity. In RA, bone destruction is caused by the enhanced activity of osteoclasts, which is mainly dependent on interleukin-17-producing helper T cells (T_H17). These findings led to the emergence and subsequent rapid evolution of the field of osteoimmunology. The scope of osteoimmunology has been extended to encompass a wide range of molecular and cellular interactions, and its framework will provide a scientific basis for future therapeutic approaches to diseases related to both of these systems.