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Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Open accessAbstract
Osteoprotegerin (OPG) is a secreted protein that inhibits osteoclast formation. In this study the physiological role of OPG is investigated by generating OPG-deficient mice. Adolescent and adult OPG-/- mice exhibit a decrease in total bone density characterized by severe trabecular and cortical bone porosity, marked thinning of the parietal bones of the skull, and a high incidence of fractures. These findings demonstrate that OPG is a critical regulator of postnatal bone mass. Unexpectedly, OPG-deficient mice also exhibit medial calcification of the aorta and renal arteries, suggesting that regulation of OPG, its signaling pathway, or its ligand(s) may play a role in the long observed association between osteoporosis and vascular calcification.
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“overexpression of OPG produced osteopetrosis, while OPG-knockout mice had a phenotype of severe osteoporosis with a high incidence of fractures”
From Pathogenesis of osteoporosis: concepts, conflicts, and prospects (2005) · cites this paper as [46]
In the citing paper
“The essential physiological role of OPG in maintaining bone mass was shown by the severe osteopenic phenotype of OPG knockout mice (124 -126).These mice exhibit increased bone turnover, cortical porosity, and reductions in cortical and cancellous bone volume and density.These deleterious changes are accompanied by spontaneous fragility fractures in the first weeks of life (124).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [124]
In the citing paper
“OPG knockout animals developed medial calcification of the aorta and renal arteries, in association with elevated bone turnover (124).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [124]
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Citations
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Self-citation
Metadata
- Authors
- Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., Boyle, W. J., & Simonet, W. S.
- Affiliations
- Amgen (United States) (US)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1998-05-01
- Volume
- 12
- Issue
- 9
- Pages
- 1260-1268
- ISSN
- 0890-9369 (ISSN-L)
- PMC
- PMC316769
- OpenAlex
- W2129651548
- Cited by
- 2,483
- References
- 42
- Citations by year
- 2026: 29 · 2025: 29 · 2024: 46 · 2023: 43 · 2022: 52 · 2021: 61 · 2020: 90 · 2019: 62 · 2018: 53 · 2017: 93 · 2016: 82 · 2015: 94 · 2014: 89 · 2013: 122 · 2012: 106
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
- Keywords
- osteoprotegerin, osteoporosis, arterial calcification, vascular calcification, osteoclastogenesis, bone mineral density, trabecular bone, cortical bone, bone porosity, fracture, renal artery calcification
- MeSH terms
- Animals, Arteries, Calcinosis, Disease Models, Animal, Female, Glycoproteins, Male, Osteoporosis, Vascular Diseases, Bone Density, In Situ Hybridization, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Gene Targeting, Mice, Osteoprotegerin
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