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Functions of RANKL/RANK/OPG in bone modeling and remodeling
Open accessAbstract
The discovery of the RANKL/RANK/OPG system in the mid 1990s for the regulation of bone resorption has led to major advances in our understanding of how bone modeling and remodeling are regulated. It had been known for many years before this discovery that osteoblastic stromal cells regulated osteoclast formation, but it had not been anticipated that they would do this through expression of members of the TNF superfamily: receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG), or that these cytokines and signaling through receptor activator of NF-kappaB (RANK) would have extensive functions beyond regulation of bone remodeling. RANKL/RANK signaling regulates osteoclast formation, activation and survival in normal bone modeling and remodeling and in a variety of pathologic conditions characterized by increased bone turnover. OPG protects bone from excessive resorption by binding to RANKL and preventing it from binding to RANK. Thus, the relative concentration of RANKL and OPG in bone is a major determinant of bone mass and strength. Here, we review our current understanding of the role of the RANKL/RANK/OPG system in bone modeling and remodeling.
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“On the other hand, another factor called osteoprotegerin (OPG), which is produced by a wide range of cells including osteoblasts, stromal cells, and gingival and periodontal fibroblasts [87–89], binds to RANKL, preventing the RANK/RANKL interaction and, consequently, inhibiting the osteoclastogenesis [87] (Figure 5).”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [87]
In the citing paper
“RANKL is routinely found as a membrane bound protein (mRANKL), but it can also be cleaved into a soluble form (sRANKL)49 or delivered via EVs.35”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [49]
In the citing paper
“In addition to osteocytes, other cells can be sources of OPG or RANKL; these cells are osteoprogenitors, osteoblasts49 or cells of the immune system (B and T cells),76 which are all simultaneously present in a BMU.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [49]
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Metadata
- Authors
- Boyce, B. F., & Xing, L.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Boyce, Brendan F.
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 473
- Issue
- 2
- Pages
- 139-146
- ISSN
- 0003-9861 (ISSN-L)
- PMC
- PMC2413418
- OpenAlex
- W1975953388
- Cited by
- 1,844
- References
- 107
- Citations by year
- 2026: 107 · 2025: 132 · 2024: 149 · 2023: 127 · 2022: 145 · 2021: 166 · 2020: 141 · 2019: 122 · 2018: 94 · 2017: 106 · 2016: 71 · 2015: 92 · 2014: 76 · 2013: 73 · 2012: 69
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Archives of Biochemistry and Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR049305, R01AR043510)
- 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
- RANK/RANKL/OPG system, bone remodeling, bone modeling, osteoclastogenesis, osteoclast activation, osteoclast survival, bone resorption, TNF superfamily, receptor activator of NF-kappaB, osteoprotegerin, bone turnover
- MeSH terms
- Animals, Bone Resorption, Cell Differentiation, Humans, Osteoclasts, Osteogenesis, Signal Transduction, Bone Remodeling, Mice, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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