Osteoprotegerin Inhibits Vascular Calcification Without Affecting Atherosclerosis in ldlr (−/−) Mice
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Background— The role of osteoprotegerin in vascular disease is unclear. Recent observational studies show that serum osteoprotegerin levels are associated with the severity and progression of coronary artery disease, atherosclerosis, and vascular calcification in patients. However, genetic and treatment studies in mice suggest that osteoprotegerin may protect against vascular calcification. Methods and Results— To test whether osteoprotegerin induces or prevents vascular disease, we treated atherogenic diet–fed ldlr (−/−) mice with recombinant osteoprotegerin (Fc-OPG) or vehicle for 5 months. Vehicle-treated mice developed significant, progressive atherosclerosis with increased plasma osteoprotegerin levels, consistent with observational studies, and ≈15% of these atherosclerotic lesions developed calcified cartilage-like metaplasia. Treatment with Fc-OPG significantly reduced the calcified lesion area without affecting atherosclerotic lesion size or number, vascular cytokines, or plasma cholesterol levels. Treatment also significantly reduced tissue levels of aortic osteocalcin, a marker of mineralization. Conclusions— These data support a role for osteoprotegerin in the vasculature as an inhibitor of calcification and a marker, rather than a mediator, of atherosclerosis.
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OPG therapy consistently suppresses vascular calcification in animal models, but data on its effects on atherogenesis or other vascular disease aspects are minimal.
“Although OPG therapy consistently suppresses vascular calcification in animal models (127, 144, 166), there are minimal data on the effects of OPG therapy on atherogenesis or other aspects of vascular disease.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [166]
In LDL receptor knockout mice on a high-fat diet, 5 months of OPG treatment significantly reduced calcified lesion area in the aorta without affecting atherosclerotic lesion size or number.
“OPG treatment significantly reduced calcified lesion area in the aorta of these mice, without affecting atherosclerotic lesion size or number (166).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [166]
OPG treatment had no effect on aortic inflammatory cytokine concentrations or plasma cholesterol levels in these mice.
“OPG had no effect on concentrations of inflammatory cytokines in the aorta or on plasma cholesterol levels.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [166]
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- Authors
- Morony, S., Tintut, Y., Zhang, Z., Cattley, R. C., Van, G., Dwyer, D., Stolina, M., Kostenuik, P. J., & Demer, L. L.
- Affiliations
- Amgen (United States) (US)
- Venue
- Circulation
- Published
- 2008-01-22
- Volume
- 117
- Issue
- 3
- Pages
- 411-420
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC2680735
- OpenAlex
- W2073733302
- Cited by
- 258
- References
- 41
- Citations by year
- 2026: 9 · 2025: 1 · 2024: 9 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 11 · 2019: 8 · 2018: 12 · 2017: 14 · 2016: 18 · 2015: 19 · 2014: 14 · 2013: 17 · 2012: 19
- FWCI
- 12.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL081202, HL-081202)
- National Institute of General Medical Sciences (T32GM065823)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Keywords
- osteoprotegerin, vascular calcification, atherosclerosis, LDL receptor knockout mice, atherogenic diet, osteocalcin, coronary artery disease, vascular disease
- MeSH terms
- Animals, Aorta, Calcinosis, Endothelium, Vascular, Receptors, LDL, Recombinant Proteins, RNA, Messenger, Vascular Diseases, Mice, Knockout, Atherosclerosis, Mice, Osteoprotegerin, RANK Ligand
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