Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption.
Abstract
Deficiency of osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor-kappaB ligand (RANKL), in mice induces osteoporosis caused by enhanced bone resorption, but also accelerates bone formation. We examined whether bone formation is coupled with bone resorption in OPG-deficient (OPG-/-) mice using risedronate, an inhibitor of bone resorption. Histomorphometric analysis showed that bone formation-related parameters (e.g. mineral apposition rate and osteoblast surface/bone surface) in OPG-/- mice sharply decreased with suppression of bone resorption by daily injection of risedronate for 30 d. OPG-/- mice exhibited high serum alkaline phosphatase activity and osteocalcin concentration, both of which were decreased to the levels in wild-type mice by the risedronate injection. Serum levels of RANKL were markedly elevated in OPG-/- mice, but were unaffected by risedronate. The ectopic bone formation induced by bone morphogenetic protein-2 implantation into OPG-/- mice was not accelerated even with a high turnover rate of bone, but attenuation of mineral density from the ectopic bone was more pronounced than that in wild-type mice. These results suggest that bone formation is coupled with bone resorption at local sites in OPG-/- mice, and that serum RANKL levels do not reflect this coupling.
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OPG knockout mice have severe osteopenia with increased bone turnover, cortical porosity, reduced cortical and cancellous bone volume and density, and spontaneous fragility fractures in early life.
“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 [126]
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References 32 · Cited by 191
- Authors
- Nakamura, M., Udagawa, N., Matsuura, S., Mogi, M., Nakamura, H., Horiuchi, H., Saito, N., Hiraoka, B. Y., Kobayashi, Y., Takaoka, K., Ozawa, H., Miyazawa, H., & Takahashi, N.
- Affiliations
- Matsumoto Dental University (JP)
- Aichi Gakuin University (JP)
- Shinshu University (JP)
- Osaka City University (JP)
- Corresponding author
- Takahashi, Naoyuki
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2003-12
- Volume
- 144
- Issue
- 12
- Pages
- 5441-5449
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2112503360
- Cited by
- 191
- References
- 32
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 10 · 2019: 9 · 2018: 3 · 2017: 9 · 2016: 8 · 2015: 9 · 2014: 1 · 2013: 8 · 2012: 6
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (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
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- osteoprotegerin, RANKL, bone formation, bone resorption, osteoporosis, risedronate, mineral apposition rate, osteocalcin, alkaline phosphatase, ectopic bone formation, BMP-2
- MeSH terms
- Risedronic Acid, Animals, Bone and Bones, Bone Resorption, Calcium, Calcium Channel Blockers, Carrier Proteins, Glycoproteins, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Mutant Strains, Osteogenesis, Phosphorus, Etidronic Acid, Osteocalcin, Transforming Growth Factor beta, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Bone Morphogenetic Proteins, Mice, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Bone Morphogenetic Protein 2
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