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Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Open accessAbstract
The ligand for osteoprotegerin has been identified, and it is a TNF-related cytokine that replaces the requirement for stromal cells, vitamin D3, and glucocorticoids in the coculture model of in vitro osteoclastogenesis. OPG ligand (OPGL) binds to a unique hematopoeitic progenitor cell that is committed to the osteoclast lineage and stimulates the rapid induction of genes that typify osteoclast development. OPGL directly activates isolated mature osteoclasts in vitro, and short-term administration into normal adult mice results in osteoclast activation associated with systemic hypercalcemia. These data suggest that OPGL is an osteoclast differentiation and activation factor. The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key extracellular regulators of osteoclast development.
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“RANKL was implicated in the fusion of osteoclast precursors into multinucleated cells (39), their differentiation into mature osteoclasts (39), their attachment to bone surfaces (12), their activation to resorb bone (9,39), and their continued survival by avoiding apoptosis (11).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [39]
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“OCs differentiate from monocyte/macrophage progenitors following M-CSF [5] and RANKL [6] stimulation.”
From PU.1 target genes undergo Tet2-coupled demethylation and DNMT3b-mediated methylation in monocyte-to-osteoclast differentiation (2013) · cites this paper as [6]
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“In the late 1990s, two independent groups discovered that the receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL), also named osteoprotegerin (OPG) ligand or osteoclast differentiation factor (ODF), is the additional factor that drives the terminal OC differentiation [67,68].”
BackgroundGiuliani, N., Colla, S., Sala, R., Moroni, M., Lazzaretti, M., La Monica, S., Bonomini, S., Hojden, M., Sammarelli, G., Barillè, S., et al. (2002) · Blood · doi:10.1182/blood-2002-04-1121 · Cited by 270
The effects of smoking on bone metabolism
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RANK ligand and osteoprotegerin in myeloma bone disease.
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Osteoprotegerin Inhibits Vascular Calcification Without Affecting Atherosclerosis in ldlr (−/−) Mice
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RANKL Expression Is Related to the Differentiation State of Human Osteoblasts
Atkins, G. J., Kostakis, P., Pan, B., Farrugia, A., Gronthos, S., Evdokiou, A., Harrison, K., Findlay, D. M., & Zannettino, A. C. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.6.1088 · Cited by 245
Metadata
- Authors
- Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., Hsu, H., Sullivan, J., Hawkins, N., Davy, E., Capparelli, C., Eli, A., Qian, Y.-X., Kaufman, S., Sarosi, I., Shalhoub, V, Senaldi, G., Guo, J., Delaney, J., & Boyle, W. J.
- Affiliations
- Amgen (United States) (US)
- Corresponding author
- Boyle, W.J
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1998-04
- Volume
- 93
- Issue
- 2
- Pages
- 165-176
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2048299560
- Cited by
- 5,439
- References
- 23
- Citations by year
- 2026: 74 · 2025: 86 · 2024: 96 · 2023: 97 · 2022: 125 · 2021: 171 · 2020: 167 · 2019: 174 · 2018: 174 · 2017: 201 · 2016: 147 · 2015: 211 · 2014: 225 · 2013: 234 · 2012: 272
- FWCI
- 61.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
- Keywords
- osteoprotegerin ligand, osteoprotegerin, osteoclastogenesis, osteoclast activation, hypercalcemia, bone remodeling
- MeSH terms
- Amino Acid Sequence, Animals, Bone Resorption, Carrier Proteins, Cell Differentiation, Cells, Cultured, Cloning, Molecular, Glycoproteins, Hematopoietic Stem Cells, Humans, Hypercalcemia, Ligands, Membrane Glycoproteins, Molecular Sequence Data, Organ Specificity, Osteoclasts, Protein Binding, Recombinant Fusion Proteins, RNA, Messenger, Macrophage Colony-Stimulating Factor, Cytokines, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Gene Expression Regulation, Developmental, Coculture Techniques, Mice, Rats, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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