Fos/AP-1 proteins in bone and the immune system.
The skeleton and the immune system share a variety of different cytokines and transcription factors, thereby mutually influencing each other. These interactions are not confined to the bone marrow cavity where bone cells and hematopoietic cells exist in proximity but also occur at locations that are target sites for inflammatory bone diseases. The newly established research area termed 'osteoimmunology' attempts to unravel these skeletal/immunological relationships. Studies towards a molecular understanding of inflammatory bone diseases from an immunological as well as a bone-centered perspective have been very successful and led to the identification of several signaling pathways that are causally involved in inflammatory bone loss. Induction of receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) signals by activated T cells and subsequent activation of the key transcription factors Fos/activator protein-1 (AP-1), NF-kappaB, and NF for activation of T cells c1 (NFATc1) are in the center of the signaling networks leading to osteoclast-mediated bone loss. Conversely, nature has employed the interferon system to antagonize excessive osteoclast differentiation, although this counteracting activity appears to be overruled under pathological conditions. Here, we focus on Fos/AP-1 functions in osteoimmunology, because this osteoclastogenic transcription factor plays a central role in inflammatory bone loss by regulating genes like NFATc1 as well as the interferon system. We also attempt to put potential therapeutic strategies for inflammatory bone diseases in perspective.
Wagner
Erwin F
EF
Research Institute of Molecular Pathology (IMP), Vienna, Austria. wagner@imp.univie.ac.at
Eferl
Robert
R
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology; D001862:Bone Resorption / Q000209:etiology; D001842:Bone and Bones / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology; D019902:Chondrocytes / Q000502:physiology; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007113:Immunity, Innate; D007249:Inflammation / Q000209:etiology; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins; D010006:Osteoblasts / Q000502:physiology; D012516:Osteosarcoma / Q000209:etiology; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011971:Receptors, Immunologic / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D011971:Receptors, Immunologic; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C110546:TYROBP protein, human; D018808:Transcription Factor AP-1