The DOI matches its Crossref record; 88 of the 88 references it cites were found in a registry or an index.
RANKL/OPG; Critical role in bone physiology
Abstract
After it was proposed that the osteoblast lineage controlled the formation of osteoclasts, cell culture methods were developed that established this to be the case. Evidence was obtained that cytokines and hormones that promote osteoclast formation act first on osteoblast lineage cells to promote the production of a membrane-bound regulator of osteoclastogenesis. This proved to be receptor activator of NF-kB ligand (RANKL) a member of the tumor necrosis factor ligand family that acts upon its receptor RANK in the hematopoietic lineage, with interaction restricted by a decoy soluble receptor osteoprotegerin (OPG), also a product of the osteoblast lineage. The physiological roles of these factors were established through genetic and pharmacological studies, have led to a new physiology of bone, with complete revision of older ideas over the last 15 years, ultimately leading to the development of new pharmaceutical agents for bone disease.
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“The most classic and well-known interaction between bone cells is that osteoblast lineage cells could secrete RANKL and induce osteoclastogenesis51.”
From Targeting Msx2 as a brake in the fusion fate of osteoclasts and an anabolic therapy in pre-clinical models of osteoporosis (2025) · cites this paper as [51]
Citations
Cites
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
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Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
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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
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Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
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Self-citationA homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
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Evidence for osteocyte regulation of bone homeostasis through RANKL expression
Nakashima, T., Hayashi, M., Fukunaga, T., Kurata, K., Oh-hora, M., Feng, J. Q., Bonewald, L. F., Kodama, T., Wutz, A., Wagner, E. F., et al. (2011) · Nature Medicine · doi:10.1038/nm.2452 · Cited by 1,778
Research works printed but not linked: 1
- Parfitt AM. Skeletal heterogeneity and the purposes of bone remodelling: Implications for the understanding of osteoporosis. In: Marcus R, Feldman D, Kelsey J, editors. Osteoporosis. San Diego, CA: Academic; 1996. p. 315–39.
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Ikebuchi, Y., Aoki, S., Honma, M., Hayashi, M., Sugamori, Y., Khan, M., Kariya, Y., Kato, G., Tabata, Y., Penninger, J. M., et al. (2018) · Nature · doi:10.1038/s41586-018-0482-7 · Cited by 557
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Metadata
- Authors
- Martin, T. J., & Sims, N. A.
- Affiliations
- The University of Melbourne (AU)
- Corresponding author
- Martin, T. John
- Venue
- Reviews in Endocrine and Metabolic Disorders
- Published
- 2015-01-04
- Volume
- 16
- Issue
- 2
- Pages
- 131-139
- ISSN
- 1389-9155 (ISSN-L)
- 1573-2606
- OpenAlex
- W1999943656
- Cited by
- 213
- References
- 88
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 18 · 2023: 19 · 2022: 12 · 2021: 23 · 2020: 29 · 2019: 25 · 2018: 21 · 2017: 26 · 2016: 9 · 2015: 2
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Reviews in Endocrine and Metabolic Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council
- National Medical Research Council
- 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 › Osteomyelitis and Bone Disorders Research
- Keywords
- RANKL, osteoprotegerin, RANK, osteoclastogenesis, osteoblast lineage, bone physiology, bone remodeling
- MeSH terms
- Animals, Bone and Bones, Humans, Mutation, Osteoblasts, Signal Transduction, Paracrine Communication, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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