Abstract
The bone is an essential organ for locomotion and protection of the body, as well as hematopoiesis and mineral homeostasis. In order to exert these functions throughout life, bone tissue undergoes a repeating cycle of osteoclastic bone resorption and osteoblastic bone formation. The osteoclast is a large, multinucleated cell that is differentiated from monocyte/macrophage lineage cells by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). RANKL transduces its signal through the signaling receptor, RANK. RANKL/RANK signaling activates NFATc1, the master regulator of osteoclastogenesis, to induce osteoclastogenic gene expression. Many types of cells express RANKL to support osteoclastogenesis depending on the biological context and the dysregulation of RANKL signaling leads to bone diseases such as osteoporosis and osteopetrosis. This review outlines the findings on osteoclast and RANKL/RANK signaling that have accumulated to date.
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Acknowledgements
This work was supported by Ichiro Kanehara Foundation, Lotte Research Promotion Grant, Takeda Science Foundation, The Uehara Memorial Foundation, Japan Agency for Medical Research and Development (AMED, award number: JP17gm0810003), Japan Society for the Promotion of Science (JSPS), Naito Foundation, Astellas Foundation for Research on Metabolic Disorders, Sumitomo Foundation, Asahi Glass Foundation, Daiichi Sankyo Foundation of Life Science, Secom Science and Technology Foundation (SSTF), Mochida Memorial Foundation for Medical and Pharmaceutical Research, Terumo Foundation and Matsui Life Social Welfare Foundation.
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Ono, T., Nakashima, T. Recent advances in osteoclast biology. Histochem Cell Biol 149, 325–341 (2018). https://doi.org/10.1007/s00418-018-1636-2
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DOI: https://doi.org/10.1007/s00418-018-1636-2