Osteoimmunology: The conceptual framework unifying the immune and skeletal systems
Abstract
The immune and skeletal systems share a variety of molecules, including cytokines, chemokines, hormones, receptors, and transcription factors. Bone cells interact with immune cells under physiological and pathological conditions. Osteoimmunology was created as a new interdisciplinary field in large part to highlight the shared molecules and reciprocal interactions between the two systems in both heath and disease. Receptor activator of NF-κB ligand (RANKL) plays an essential role not only in the development of immune organs and bones, but also in autoimmune diseases affecting bone, thus effectively comprising the molecule that links the two systems. Here we review the function, gene regulation, and signal transduction of osteoimmune molecules, including RANKL, in the context of osteoclastogenesis as well as multiple other regulatory functions. Osteoimmunology has become indispensable for understanding the pathogenesis of a number of diseases such as rheumatoid arthritis (RA). We review the various osteoimmune pathologies, including the bone destruction in RA, in which pathogenic helper T cell subsets [such as IL-17-expressing helper T (Th17) cells] induce bone erosion through aberrant RANKL expression. We also focus on cellular interactions and the identification of the communication factors in the bone marrow, discussing the contribution of bone cells to the maintenance and regulation of hematopoietic stem and progenitors cells. Thus the time has come for a basic reappraisal…
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IL-17 produced by T17 lymphocytes serves as a potent osteoclastogenic cytokine in association with inflammatory joint diseases such as rheumatoid arthritis.
“In association with inflammatory joint diseases such as rheumatoid arthritis, IL-17 produced by T17 lymphocytes serves as a potent osteoclastogenic cytokine [1].”
From Osteoclasts and Microgravity (2020) · cites this paper as [1]
A number of physiopathological conditions are characterized by excessive osteoclast activity, including menopause, juvenile Paget's disease of bone, inflammatory joint diseases, bone cancers such as multiple myeloma, and glucocorticoid therapy.
“a number of physiopathological conditions are characterized by excessive osteoclast activity. These include but are not limited to menopause, juvenile Paget’s disease of bone, inflammatory joint diseases, bone cancers such as multiple myeloma, and glucocorticoid therapy [1,2]”
From Osteoclasts and Microgravity (2020) · cites this paper as [1]
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- Authors
- Okamoto, K., Nakashima, T., Shinohara, M., Negishi-Koga, T., Komatsu, N., Terashima, A., Sawa, S., Nitta, T., & Takayanagi, H.
- Affiliations
- SHOWA Medical University (JP)
- Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan; Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO), Tokyo, Japan; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Tokyo, Japan;...
- ORCID
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2017-10-01
- Volume
- 97
- Issue
- 4
- Pages
- 1295-1349
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2747893584
- Cited by
- 534
- References
- 40
- Citations by year
- 2026: 47 · 2025: 72 · 2024: 80 · 2023: 67 · 2022: 69 · 2021: 55 · 2020: 65 · 2019: 47 · 2018: 30 · 2017: 2
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (16K14648, 17K19582, 15H05653, 15K15149, 16H05506, 17H04050, 15H05703, 16H05202)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Keywords
- osteoimmunology, RANKL, osteoclastogenesis, rheumatoid arthritis, Th17 cells, IL-17, bone erosion, bone marrow, hematopoietic stem and progenitor cells, signal transduction, gene expression regulation
- MeSH terms
- Allergy and Immunology, Animals, Arthritis, Rheumatoid, Cell Communication, Hematopoietic Stem Cells, Humans, Immunity, Osteoclasts, Skeleton, Signal Transduction, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Osteology
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