Fos/AP‐1 proteins in bone and the immune system
Abstract
Summary: 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)‐κB ligand (RANKL) signals by activated T cells and subsequent activation of the key transcription factors Fos/activator protein‐1 (AP‐1), NF‐κB, 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.
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The SNP rs242983646 is predicted to disrupt a c-fos binding site.
“Disruption of c-fos binding site (involved in cell proliferation, growth and survival pathways, including bone and immune cells [88])”
From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [88]
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“rs242983646 5:119860887 A/C Intron variant Disruption of c-fos binding site (involved in cell proliferation, growth and survival pathways, including bone and immune cells [88])”
Background
- Authors
- Wagner, E. F., & Eferl, R.
- Affiliations
- Research Institute of Molecular Pathology (AT)
- Ludwig Boltzmann Institute for Cancer Research (AT)
- Corresponding author
- Wagner, Erwin F.
- Venue
- Immunological Reviews
- Publisher
- Wiley
- Published
- 2005-11-22
- Volume
- 208
- Issue
- 1
- Pages
- 126-140
- ISSN
- 0105-2896 (ISSN-L)
- 1600-065X
- OpenAlex
- W1982581668
- Cited by
- 537
- References
- 9
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 23 · 2023: 25 · 2022: 29 · 2021: 33 · 2020: 23 · 2019: 26 · 2018: 19 · 2017: 26 · 2016: 22 · 2015: 26 · 2014: 29 · 2013: 27 · 2012: 29
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- osteoimmunology, inflammatory bone loss, osteoclastogenesis, RANKL signaling, NF-κB, NFATc1, interferon system, T cell activation, bone-immune crosstalk
- MeSH terms
- Animals, Arthritis, Rheumatoid, Bone and Bones, Bone Resorption, Carrier Proteins, Humans, Immune System, Immunity, Innate, Inflammation, Membrane Glycoproteins, Membrane Proteins, Osteoblasts, Receptors, Immunologic, Osteosarcoma, Proto-Oncogene Proteins c-fos, Transcription Factor AP-1, Chondrocytes, Adaptor Proteins, Signal Transducing, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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