Dopamine receptor signaling regulates human osteoclastogenesis

Abstract

Although the central nervous system and the neurotransmitters are known to control not only the immune system but also the homeostasis of bone mass, their pathological relevance to bone disorders remains unclear. Osteoclasts in the synovium of rheumatoid arthritis (RA) play an important role in bone destruction. It is known that increased sympathetic nervous activity increases both diŠerentiation and function of osteoclasts, which leads to bone loss. Dopamine, a major neurotransmitter, transmits signals via five diŠerent seven-transmembrane G protein-coupled receptors termed D1 to D5. We previously reported that dopamine plays an important role in IL-6-IL-17 axis and subsequent joint destruction in RA. The major source of dopamine in the synovial tissue of RA was dendritic cells (DCs) that stored and secreted dopamine. Dopamine released by DCs bounded to D1-like dopamine receptors on T cells and induced activation of cAMP and diŠerentiation to Th17 cells via IL-6 production We here overview the interplay among the immune system, bone metabolism and neurologic system shedding light upon dopaminergic signals upon osteoclastogenesis. © 2013 The Japan Society for Clinical Immunology.