A chimeric form of osteoprotegerin inhibits hypercalcemia and bone resorption induced by IL-1β, TNF-α, PTH, PTHrP, and 1,25(OH)2D3.
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Osteoprotegerin (OPG) is a secreted protein that inhibits osteoclast formation and activity and appears to be a critical regulator of bone mass and metabolism. In the current study, mice were challenged with various cytokines and hormones (interleukin-1β, tumor necrosis factor-α, parathyroid hormone, parathyroid hormone-related protein, and 1α,25-dihydroxyvitamin D3) that are known to increase bone resorption and cause hypercalcemia and treated concurrently with either a recombinant chimeric Fc fusion form of human OPG, with enhanced biological activity (cOPG) (2.5 mg/kg/day) or vehicle. Mice receiving these bone-resorbing factors became hypercalcemic by day 3 after commencing treatment and had increased bone resorption as evidenced by elevated osteoclast numbers on day 5. Concurrent cOPG treatment prevented hypercalcemia (p < 0.05) and maintained osteoclast numbers in the normal range (p < 0.001). The demonstration that cOPG can inhibit bone resorption suggests that this molecule may be useful in the treatment of diseases including hyperparathyroidism, humoral hypercalcemia of malignancy, osteoporosis, and inflammatory bone disease, which are characterized, in part, by increases in osteoclastic bone resorption.
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OPG treatment of mice fully prevents the proresorptive effects of IL-1 and TNF-α.
“In support of the latter notion, OPG treatment of mice was able to fully prevent the proresorptive effects of IL-1 and TNF-␣ (21).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [21]
OPG prevents the ability of proresorptive agents (IL-1, TNF-α, PTH, PTHrP, vitamin D) to increase bone resorption in mice, consistent with those agents increasing resorption by raising the RANKL:OPG ratio.
“OPG prevents the ability of proresorptive agents (IL-1, TNF-␣, PTH, PTHrP, vitamin D) to increase bone resorption in mice (21), which is consistent with the interpretation that those agents increase bone resorption by increasing the RANKL:OPG ratio.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [21]
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- Authors
- Morony, S., Capparelli, C., Lee, R., Shimamoto, G., Boone, T., Lacey, D. L., & Dunstan, C. R.
- Affiliations
- Amgen (United States) (US)
- Corresponding author
- Dunstan, Colin R.
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-09-01
- Volume
- 14
- Issue
- 9
- Pages
- 1478-1485
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2050716165
- Cited by
- 187
- References
- 43
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 2 · 2020: 3 · 2019: 4 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 7
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- 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
- osteoprotegerin, hypercalcemia, bone resorption, osteoclasts, IL-1β, TNF-α, parathyroid hormone, parathyroid hormone-related protein, 1,25-dihydroxyvitamin D3, hyperparathyroidism, humoral hypercalcemia of malignancy, osteoporosis, inflammatory bone disease, bone metabolism
- MeSH terms
- Animals, Bone and Bones, Bone Resorption, Calcitriol, Calcium, Cell Count, Glycoproteins, Humans, Hypercalcemia, Interleukin-1, Isomerism, Male, Osteoclasts, Parathyroid Hormone, Proteins, Radiography, Tumor Necrosis Factor-alpha, Weight Loss, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Parathyroid Hormone-Related Protein, Mice, Osteoprotegerin
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