RANKL biology: bone metabolism, the immune system, and beyond
Top Cited Papers
Open Access
- 7 February 2020
- journal article
- review article
- Published by Springer Science and Business Media LLC in Inflammation and Regeneration
- Vol. 40 (1), 1-16
- https://doi.org/10.1186/s41232-019-0111-3
Abstract
Receptor activator of NF-kappa B (RANK) ligand (RANKL) induces the differentiation of monocyte/macrophage-lineage cells into the bone-resorbing cells called osteoclasts. Because abnormalities in RANKL, its signaling receptor RANK, or decoy receptor osteoprotegerin (OPG) lead to bone diseases such as osteopetrosis, the RANKL/RANK/OPG system is essential for bone resorption. RANKL was first discovered as a T cell-derived activator of dendritic cells (DCs) and has many functions in the immune system, including organogenesis, cellular development. The essentiality of RANKL in the bone and the immune systems lies at the root of the field of "osteoimmunology." Furthermore, this cytokine functions beyond the domains of bone metabolism and the immune system, e.g., mammary gland and hair follicle formation, body temperature regulation, muscle metabolism, and tumor development. In this review, we will summarize the current understanding of the functions of the RANKL/RANK/OPG system in biological processes.Keywords
Funding Information
- Japan Society for the Promotion of Science
- Precursory Research for Embryonic Science and Technology
- Japan Agency for Medical Research and Development
- Daiichi Sankyo Foundation of Life Science
- Japan Rheumatism Foundation
- Kanzawa Medical Research Foundation
- Life Science Foundation of Japan
- Lotte Research promotion grant
- Meiji Yasuda Life Foundation of Health and Welfare
- Mitsui Life Social Foundation
- Naito Foundation
- Nakatomi Foundation
- Ono Medical Research Foundation
- Secom Science and Technology Foundation
- Suzuken Memorial Foundation
- Takeda Science Foundation
- Asahi Glass Foundation
- Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care
- Sumitomo Foundation
- Uehara Memorial Foundation
- Tokyo Medical and Dental University
This publication has 113 references indexed in Scilit:
- Rank Signaling Links the Development of Invariant γδ T Cell Progenitors and Aire+ Medullary EpitheliumImmunity, 2012
- Matrix-embedded cells control osteoclast formationNature Medicine, 2011
- Prostaglandin E2–prostoglandin E receptor subtype 4 (EP4) signaling mediates UV irradiation-induced systemic immunosuppressionProceedings of the National Academy of Sciences of the United States of America, 2011
- Receptor activator of NF-κB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unitProceedings of the National Academy of Sciences of the United States of America, 2011
- Emerging therapeutic opportunities for skeletal restorationNature Reviews Drug Discovery, 2011
- Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancerNature, 2010
- Human Osteoclast-Poor Osteopetrosis with Hypogammaglobulinemia due to TNFRSF11A (RANK) MutationsAmerican Journal of Human Genetics, 2008
- Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systemsNature Reviews Immunology, 2007
- Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destructionThe Journal of Experimental Medicine, 2006
- Regulation of cancer cell migration and bone metastasis by RANKLNature, 2006