Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems
Kazuo Okamoto,Tomoki Nakashima,Masahiro Shinohara,Takako Negishi-Koga,Noriko Komatsu,Asuka Terashima,Shinichiro Sawa,Takeshi Nitta,Hiroshi Takayanagi +8 more
TLDR
The function, gene regulation, and signal transduction of osteoimmune molecules, including RANKL, in the context of osteoclastogenesis as well as multiple other regulatory functions are reviewed.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 of the framework for understanding both the immune and bone systems. The concept of a unified osteoimmune system will be absolutely indispensable for basic and translational approaches to diseases related to bone and/or the immune system.read more
Citations
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Journal ArticleDOI
Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies.
TL;DR: Current treatment strategies for rheumatoid arthritis are reviewed and how such insights could ultimately lead to the earlier diagnosis of RA - as well as providing new opportunities for drug treatment and prevention through behavioral changes in high-risk individuals.
Journal ArticleDOI
Osteoimmunology: evolving concepts in bone–immune interactions in health and disease
TL;DR: It is well known that immune cells can have profound effects on bone cells, but this interaction is not unidirectional, so Tsukasaki and Takayanagi explore the reciprocal dialogue between bone cells and immune cells during health and disease.
Journal ArticleDOI
Recent advances in osteoclast biology
TL;DR: This review outlines the findings on osteoclast and RANKL/RANK signaling that have accumulated to date and indicates that the dysregulation of RANKl signaling leads to bone diseases such as osteoporosis and osteopetrosis.
Journal ArticleDOI
The integration of inflammaging in age-related diseases.
TL;DR: The concept of inflammaging is described, being a chronic, systemic, low grade and therefore for a long time subclinical, inflammatory process, and how it is integrated in the context of ARD.
Journal ArticleDOI
RANKL biology: bone metabolism, the immune system, and beyond
Takehito Ono,Takehito Ono,Mikihito Hayashi,Mikihito Hayashi,Fumiyuki Sasaki,Fumiyuki Sasaki,Tomoki Nakashima,Tomoki Nakashima +7 more
TL;DR: The current understanding of the functions of the RANKL/RANK/OPG system in biological processes is summarized.
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