The DOI matches its Crossref record; 107 of the 107 references it cites were found in a registry or an index.
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]
Citations
Cites
Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439
Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80209-3 · Cited by 5,130
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., & Karsenty, G. (1997) · Cell · doi:10.1016/s0092-8674(00)80257-3 · Cited by 4,246
Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., Shimizu, Y., Bronson, R. T., Gao, Y.-H., Inada, M., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80258-5 · Cited by 4,244
Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3597 · Cited by 4,224
Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J. M., Behringer, R. R., & de Crombrugghe, B. (2002) · Cell · doi:10.1016/s0092-8674(01)00622-5 · Cited by 3,608
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
Kong, Y.-Y., Yoshida, H., Sarosi, I., Tan, H.-L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A. J., Van, G., Itie, A., et al. (1999) · Nature · doi:10.1038/16852 · Cited by 3,351
Takayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J.-I., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00369-6 · Cited by 2,701
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., et al. (1998) · Genes & Development · doi:10.1101/gad.12.9.1260 · Cited by 2,483
Flagged first, then by citations
Research works printed but not linked: 9
- Usui, 2007, J. Bone Miner. Res.
- Wong, 2000, J. Bone Miner. Res., 15, 2293
- Kearns, 2007, Endocr. Rev.
- Hikita, 2006, J. Biol. Chem.
- Bai, 2007, J. Biol. Chem.
- Sammartino, 2005, J. Endocrinol. Invest., 28, 80
- Fretz, 2007, Mol. Endocrinol.
- Yao, 2006, JBMR, 21, S262
- Guo, 2007, JBMR, 22, S30
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International Journal of Molecular Sciences
Soni, N., Ross, A., Nookaew, I., Scheers, N., Gabrielsson, B., & Sandberg, A.-S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms · Cited by 10,136
Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells
Florencio-Silva, R., Sasso, G. R. D. S., Sasso-Cerri, E., Simões, M. J., & Cerri, P. S. (2015) · BioMed Research International · doi:10.1155/2015/421746 · Cited by 2,044
Osteoblast–osteoclast interactions
Chen, X., Wang, Z., Duan, N., Zhu, G., Schwarz, E. M., & Xie, C. L. (2017) · Connective Tissue Research · doi:10.1080/03008207.2017.1290085 · Cited by 905
Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms
Booth, F. W., Roberts, C. K., Thyfault, J. P., Ruegsegger, G. N., & Toedebusch, R. G. (2017) · Physiological Reviews · doi:10.1152/physrev.00019.2016 · Cited by 696
Rogers, L. C., Frykberg, R. G., Armstrong, D. G., Boulton, A. J. M., EDMONDS, M. E., Van, G. H., Hartemann, A., Game, F. L., Jeffcoate, W. J., Jirkovská, A., et al. (2011) · Diabetes Care · doi:10.2337/dc11-0844 · Cited by 597
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
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