The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Minireview: The OPG/RANKL/RANK System
Abstract
The identification of the OPG/RANKL/RANK system as the dominant, final mediator of osteoclastogenesis represents a major advance in bone biology. It ended a long-standing search for the specific factor produced by preosteoblastic/stromal cells that was both necessary and sufficient for osteoclast development. The initial cloning and characterization of OPG as a soluble, decoy receptor belonging to the TNF receptor superfamily was the first step that eventually led to an unraveling of this system. Soon thereafter, the molecule blocked by OPG, initially called OPG-ligand/osteoclast differentiating factor (ODF) and subsequently RANKL, was identified as the key mediator of osteoclastogenesis in both a membrane-bound form expressed on preosteoblastic/stromal cells as well as a soluble form. RANKL, in turn, was shown to bind its receptor, RANK, on osteoclast lineage cells. The decisive role played by these factors in regulating bone metabolism was demonstrated by the findings of extremes of skeletal phenotypes (osteoporosis vs. osteopetrosis) in mice with altered expression of these molecules. Over the past several years, work has focused on identifying the factors regulating this system, the signaling mechanisms involved in the RANKL/RANK pathway, and finally, potential alterations in this system in metabolic bone disorders, from the extremely common (i.e. postmenopausal osteoporosis) to the rare (i.e. familial expansile osteolysis).
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“Thus, the ratio between the levels of OPG and RANKL is a key factor in the control of osteoclast activation and bone resorption (120).”
From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [120]
In the citing paper
“OPG acts as a decoy receptor for osteoclast activating factor and a receptor activator of RANKL and impairs osteoclast function [158].”
From Emerging role of liver-bone axis in osteoporosis (2024) · cites this paper as [158]
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Cites
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
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Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
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Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
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OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
Kong, Y.-Y., Yoshida, H., Sarosi, I., Tan, H.-L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A. J., Van, G., Itie, A., et al. (1999) · Nature · doi:10.1038/16852 · Cited by 3,351
Manolagas, S. C. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.2.0395 · Cited by 2,639
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., et al. (1998) · Genes & Development · doi:10.1101/gad.12.9.1260 · Cited by 2,483
A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
Anderson, D. M., Maraskovsky, E., Billingsley, W. L., Dougall, W. C., Tometsko, M. E., Roux, E. R., Teepe, M. C., DuBose, R. F., Cosman, D., & Galibert, L. (1997) · Nature · doi:10.1038/36593 · Cited by 2,290
Kong, Y.-Y., Feige, U., Sarosi, I., Bolon, B., Tafuri, A., Morony, S., Capparelli, C., Li, J., Elliott, R., McCabe, S., et al. (1999) · Nature · doi:10.1038/46303 · Cited by 1,856
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Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670
Estrogen deficiency and bone loss: an inflammatory tale
Weitzmann, M. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28550 · Cited by 990
The aging of Wolff’s “law”: Ontogeny and responses to mechanical loading in cortical bone
Pearson, O. M., & Lieberman, D. E. (2004) · American Journal of Physical Anthropology · doi:10.1002/ajpa.20155 · Cited by 745
Role of RANK ligand in mediating increased bone resorption in early postmenopausal women
Eghbali-Fatourechi, G., Khosla, S., Sanyal, A., Boyle, W. J., Lacey, D. L., & Riggs, B. L. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17215 · Cited by 825
Self-citationZhou, Y., Yang, D., Yang, Q., Lv, X., Huang, W., Zhou, Z., Wang, Y., Zhang, Z., Yuan, T., Ding, X., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-20059-6 · Cited by 672
Metadata
- Authors
- Khosla, S.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Khosla, Sundeep
- ORCID
- Khosla, Sundeep
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2001-12
- Volume
- 142
- Issue
- 12
- Pages
- 5050-5055
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2168451480
- Semantic Scholar
- eedbd21edfd4c221424281c1f92426223aaac5db
- Cited by
- 1,515
- References
- 58
- Citations by year
- 2026: 20 · 2025: 37 · 2024: 36 · 2023: 27 · 2022: 46 · 2021: 49 · 2020: 53 · 2019: 67 · 2018: 79 · 2017: 72 · 2016: 70 · 2015: 78 · 2014: 80 · 2013: 97 · 2012: 81
- FWCI
- 14.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service
- National Institute on Aging (AG 04875, P01AG004875)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- osteoclastogenesis, RANKL, RANK, osteoprotegerin, TNF receptor superfamily, bone metabolism, osteoporosis, osteopetrosis, postmenopausal osteoporosis, RANK/RANKL signaling, metabolic bone disease
- MeSH terms
- Animals, Bone Diseases, Metabolic, Carrier Proteins, Cell Division, Glycoproteins, Humans, Membrane Glycoproteins, Osteoclasts, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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