The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.
Osteoclast differentiation and activation
Abstract
Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.
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“Because TRAIL and RANKL are known to regulate osteoclast differentiation and survival (33–35), these findings suggest that increased RANK (tumor necrosis factor receptor superfamily member 11a) signaling may be involved in the regulation of bone growth and remodeling induced by ACVR2B/Fc.”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [33]
In the citing paper
“Because TRAIL and RANKL are known to regulate osteoclast differentiation and survival (33–35), these findings suggest that increased RANK (tumor necrosis factor receptor superfamily member 11a) signaling may be involved in the regulation of bone growth and remodeling induced by ACVR2B/Fc.”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [33]
Citations
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“Activation of these RANKL-induced signaling pathways induces the expression and activation of c-Fos and nuclear factor of activated T cells (NFAT) c1, which are known to be critical regulators of osteoclast differentiation [Boyle et al., 2003; Feng, 2005].”
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“Its cognate high affinity transmembrane receptor, receptor activator of nuclear factor kappa B (RANK) is expressed in both mature osteoclasts and their circulating precursor cells belonging to the monocytic/ macrophagic lineage (Boyle et al., 2003).”
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“In addition, increased expression of receptor activator of NF-k B ligand (RANKL), by stromal cells or osteoblasts, stimulates its cognate receptor RANK on the osteoclast progenitor cells causing an unique osteoclast differentiation signal (Teitelbaum 2000, Boyle et al .”
Role and Regulation of Transcription Factors in Osteoclastogenesis
Jiang, T., Xia, T., Qiao, F., Wang, N., Jiang, Y., & Xin, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216175 · Cited by 60
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“Osteoclasts are a specific polykaryon derived from monocyte/macrophage precursor cells/hematopoietic stem cells (HSCs) [3].”
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“Activation of RANK/ RANKL signaling pathway induces downstream signaling cascades that upregulate the expression of specific genes involved in osteoclast differentiation, activation and survival [22,31].”
BackgroundRelationship between saturated fatty acids and periodontal disease
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“Excess osteoclastic activity leads to an imbalance in bone remodeling which favors resorption associated with periodontal disease (Boyle et al., 2003).”
BackgroundConstitutive activation of RANK disrupts mammary cell fate leading to tumorigenesis
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“The differentiation and activation of osteoclasts are tightly regulated by osteoblasts (1, 2).”
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NOTCH2 Hajdu-Cheney Mutations Escape SCFFBW7-Dependent Proteolysis to Promote Osteoporosis
Fukushima, H., Shimizu, K., Watahiki, A., Hoshikawa, S., Kosho, T., Oba, D., Sakano, S., Arakaki, M., Yamada, A., Nagashima, K., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.10.018 · Cited by 46
“Bone metabolism and homeostasis are regulated by the boneremodeling activities of osteoblasts and osteoclasts, and an imbalance in these activities leads to the development of various skeletal disorders (Boyle et al., 2003; Rodan and Martin, 2000).”
BackgroundSialylation of TLR2 initiates osteoclast fusion
Dou, C., Zhen, G., Dan, Y., Wan, M., Limjunyawong, N., & Cao, X. (2022) · Bone Research · doi:10.1038/s41413-022-00186-0 · Cited by 46
“Together, M-CSF and RANKL effectively induce the expression of osteoclast lineagespecific genes and lead to the development of osteoclast maturation marked by cell fusion-mediated multinucleation.(1,3) The requirement for cell fusion in osteoclast formation has been studied for decades, and numerous fusogenic molecule…”
BackgroundThe effect of whole body vibration on fracture healing - a systematic review
Department of Orthopaedics and Traumatology, P. O. W. H., Wang, J., Leung, K., Chow, S., & Cheung, W. (2017) · European Cells and Materials · doi:10.22203/ecm.v034a08 · Cited by 45
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“RANKL binding to RANK induces NF- B activity and the expression of genes that characterize the osteoclast lineage.((3)) RANKL also enhances the activity and survival of mature osteoclasts.”
BackgroundTransmigration: A New Property of Mature Multinucleated Osteoclasts
Saltel, F., Chabadel, A., Zhao, Y., Lafage-Proust, M.-H., Clézardin, P., Jurdic, P., & Bonnelye, E. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.060821 · Cited by 41
“indicated that (1) the cortical and cancellous bone were almost completely destroyed and replaced by tumor cells that filled the bone marrow cavity (Fig.”
BackgroundMalignant Autosomal Recessive Osteopetrosis Caused by Spontaneous Mutation of Murine Rank
Kapur, R. P., Yao, Z., Iida, M. H., Clarke, C. M., Doggett, B., Xing, L., & Boyce, B. F. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040713 · Cited by 39
“groups based on whether osteoclasts are absent versus present, but dysfunctional.((5,6))”
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“This biological system can influence osteoclastogenesis and bone resorption regulating the biosynthesis of RANKL and osteoprotegerin (OPG) by stromalosteoblastic cells [8].”
BackgroundResultSTAC2 negatively regulates osteoclast formation by targeting the RANK signaling complex
Jeong, E., Choi, H. K., Park, J. H., & Lee, S. Y. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0048-5 · Cited by 35
Unexpected Bone Formation Produced by RANKL Blockade
Portal-Núñez, S., Mediero, A., Esbrit, P., Sánchez-Pernaute, O., Largo, R., & Herrero-Beaumont, G. (2017) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2017.06.003 · Cited by 32
Saltman, L. H., Javed, A., Ribadeneyra, J., Hussain, S., Young, D. W., Osdoby, P., Amcheslavsky, A., van Wijnen, A. J., Stein, J. L., Stein, G. S., et al. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20329 · Cited by 28
“This major breakthrough led to a greater understanding of the mechanisms controlling osteoclast differentiation and activity under normal biological and pathological conditions (Boyle et al., 2003; Teitelbaum and Ross, 2003).”
BackgroundInfluentialThe Role of Toll-Like Receptors in Osteoclastogenesis
Yim, M. (2020) · Journal of Bone Metabolism · doi:10.11005/jbm.2020.27.4.227 · Cited by 28
“Two indispensable factors are required for osteoclast differentiation: receptor activator of nuclear factor (NF)-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF).[3,4] M‐CSF is essential for the proliferation and survival of osteoclast precursors and guides the early step of osteoclastogenesis.”
BackgroundA review of mathematical modeling of bone remodeling from a systems biology perspective
Cook, C. V., Lighty, A. M., Smith, B. J., & Ford Versypt, A. N. (2024) · Frontiers in Systems Biology · doi:10.3389/fsysb.2024.1368555 · Cited by 25
The induction of RANKL molecule clustering could stimulate early osteoblast differentiation
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SIRT2 deficiency prevents age-related bone loss in rats by inhibiting osteoclastogenesis
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“During osteoclastogenesis, all osteoclast target molecules are stimulated by the activation of RANK (29, 30).”
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BackgroundPeroxidase enzymes inhibit osteoclast differentiation and bone resorption
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“…present study subsequently measured caspase-3 activity and protein expression levels and, in accordance with the above findings, IMD markedly attenuated caspase-3 activity and Osteoclasts originate from the monocyte/macrophage hematopoietic lineages and are responsible for bone resorption (26,27).”
Nrf2 signaling pathway: focus on oxidative stress in osteoporosis
Gu, H.-Y., Liu, N., Lin, F.-X., & Yin, J. (2025) · Osteoporosis International · doi:10.1007/s00198-025-07592-0 · Cited by 10
Aging and menopause reprogram osteoclast precursors for aggressive bone resorption
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Metadata
- Authors
- Boyle, W. J., Simonet, W. S., & Lacey, D. L.
- Affiliations
- Amgen (United States) (US)
- Corresponding author
- Boyle, William J.
- ORCID
- Boyle, William J.
- Venue
- Nature
- Published
- 2003-05
- Volume
- 423
- Issue
- 6937
- Pages
- 337-342
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2093252878
- Cited by
- 6,670
- References
- 77
- Citations by year
- 2026: 240 · 2025: 269 · 2024: 294 · 2023: 357 · 2022: 349 · 2021: 404 · 2020: 376 · 2019: 381 · 2018: 371 · 2017: 324 · 2016: 311 · 2015: 332 · 2014: 352 · 2013: 315 · 2012: 336
- FWCI
- 11.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- 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
- osteoclasts, osteoclastogenesis, bone resorption, monocyte/macrophage lineage, bone matrix degradation, hormonal regulation of bone, osteoporosis
- MeSH terms
- Animals, Bone Resorption, Carrier Proteins, Cell Differentiation, Glycoproteins, Humans, Membrane Glycoproteins, Osteoclasts, Osteoporosis, Signal Transduction, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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