Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand.
Open accessAbstract
A receptor that mediates osteoprotegerin ligand (OPGL)-induced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cDNA library and is identical to the tumor necrosis factor receptor (TNFR) family member RANK. The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo . Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo . Furthermore, polyclonal Ab against the RANK extracellular domain promotes osteoclastogenesis in bone marrow cultures suggesting that RANK activation mediates the effects of OPGL on the osteoclast pathway. These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells.
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RANK-Fc transgenic animals resemble OPG transgenics in having high bone mass, normal bone shape, and normal tooth eruption.
“Similar to OPG transgenic animals, RANK-Fc transgenic animals had high bone mass, normal bone shape, and normal tooth eruption.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [72]
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Osteoprotegerin expression in dendritic cells increases with maturation and is NF‐κB‐dependent
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Bone circuitry and interorgan skeletal crosstalk
Zaidi, M., Kim, S.-M., Mathew, M., Korkmaz, F., Sultana, F., Miyashita, S., Gumerova, A. A., Frolinger, T., Moldavski, O., Barak, O., et al. (2023) · eLife · doi:10.7554/elife.83142 · Cited by 45 · see citing works
Plasma osteoprotegerin levels are decreased in smoker chronic periodontitis patients
Özçaka, Ö., Nalbantsoy, A., Köse, T., & Buduneli, N. (2010) · Australian Dental Journal · doi:10.1111/j.1834-7819.2010.01261.x · Cited by 36 · see citing works
RANKL/RANK pathway and its inhibitor RANK-Fc in uterine leiomyoma growth
Ikhena, D. E., Liu, S., Kujawa, S., Esencan, E., Coon, J. S., Robins, J., Bulun, S. E., & Yin, P. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-01585 · Cited by 26 · see citing works
Osteoprotegerin ameliorates sciatic nerve crush induced bone loss.
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- Authors
- Hsu, H., Lacey, D. L., Dunstan, C. R., Solovyev, I., Colombero, A., Timms, E., Tan, H.-L., Elliott, G., Kelley, M. J., Sarosi, I., Wang, L., Xia, X.-Z., Elliott, R., Chiu, L., Black, T., Scully, S., Capparelli, C., Morony, S., Shimamoto, G., Bass, M. B., & Boyle, W. J.
- Affiliations
- Amgen (United States) (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-03-30
- Volume
- 96
- Issue
- 7
- Pages
- 3540-3545
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC22329
- OpenAlex
- W2106766464
- Cited by
- 1,636
- References
- 22
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 21 · 2023: 27 · 2022: 34 · 2021: 31 · 2020: 46 · 2019: 51 · 2018: 50 · 2017: 41 · 2016: 35 · 2015: 53 · 2014: 64 · 2013: 67 · 2012: 79
- FWCI
- 25.42
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- RANK, osteoprotegerin ligand, osteoclastogenesis, osteoclast activation, TNF receptor superfamily, osteopetrosis, RANK signaling
- MeSH terms
- Animals, Bone Development, Carrier Proteins, Cell Differentiation, Cell Line, Cloning, Molecular, Glycoproteins, Humans, Immunoglobulin G, Male, Membrane Glycoproteins, Mice, Inbred Strains, Mice, Transgenic, Osteoclasts, Osteogenesis, Recombinant Fusion Proteins, Recombinant Proteins, Transcription, Genetic, Transfection, Signal Transduction, Calcium-Calmodulin-Dependent Protein Kinases, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Gene Expression Regulation, Developmental, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, Mice, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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