The origins and formation of bone-resorbing osteoclasts
Abstract
Osteoclasts (OCLs) are hematopoietic cells whose physiological function is to degrade bone. OCLs are key players in the processes that determine and maintain the mass, shape, and physical properties of bone. OCLs adhere to bone tightly and degrade its matrix by secreting protons and proteases onto the underlying surface. The combination of low pH and proteases degrades the mineral and protein components of the matrix and forms a resorption pit; the degraded material is internalized by the cell and then secreted into the circulation. Insufficient or excessive activity of OCLs can lead to significant changes in bone and either cause or exacerbate symptoms of diseases, as in osteoporosis, osteopetrosis, and cancer-induced bone lysis. OCLs are derived from monocyte-macrophage precursor cells whose origins are in two distinct embryonic cell lineages - erythromyeloid progenitor cells of the yolk sac, and hematopoietic stem cells. OCLs are formed in a multi-stage process that is induced by the cytokines M-CSF and RANKL, during which the cells differentiate, fuse to form multi-nucleated cells, and then differentiate further to become mature, bone-resorbing OCLs. Recent studies indicate that OCLs can undergo fission in vivo to generate smaller cells, called "osteomorphs", that can be "re-cycled" by fusing with other cells to form new OCLs. In this review we describe OCLs and discuss their cellular origins and the cellular and molecular events that drive osteoclastogenesis.
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M-CSF and RANKL induce BMMs to proliferate, fuse, and differentiate into multinuclear osteoclasts.
“Induced by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL), bone marrow monocytes/macrophages (BMMs) could proliferate, fuse, and eventually differentiate into multi-nuclear osteoclasts8.”
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 [8]
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Shemesh, M., Addadi, L., & Geiger, B. (2017) · Journal of The Royal Society Interface · doi:10.1098/rsif.2016.0958 · Cited by 23 · see citing works
Mechanisms of RANKL delivery to the osteoclast precursor cell surface
Honma, M., Ikebuchi, Y., & Suzuki, H. (2020) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-020-01157-3 · Cited by 23 · see citing works
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Ma, Q., Wang, S., Xue, H., Ni, L., Yuan, P., Shen, Y., Zheng, B., Wang, Q., Zhang, J., Wang, H., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61938-0 · Cited by 15 · see citing works
- Authors
- Elson, A., Anuj, A., Barnea-Zohar, M., & Reuven, N.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Elson, Ari
- Venue
- Bone
- Publisher
- Elsevier BV
- Published
- 2022-11
- Volume
- 164
- Pages
- 116538
- ISSN
- 1873-2763 (ISSN-L)
- 8756-3282
- OpenAlex
- W4292787268
- Cited by
- 95
- References
- 208
- Citations by year
- 2026: 19 · 2025: 30 · 2024: 24 · 2023: 20 · 2022: 2
- FWCI
- 6.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Bone (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation (1734/20)
- Deutsche Forschungsgemeinschaft (Tu220/12)
- Weizmann Institute of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- osteoclasts, osteoclastogenesis, bone resorption, osteoclast origin, hematopoietic stem cells, yolk sac, macrophage colony-stimulating factor, RANKL, osteoclast fusion, osteoporosis, osteopetrosis, bone remodeling
- MeSH terms
- Bone Resorption, Cell Differentiation, Cells, Cultured, Humans, Osteoclasts, Peptide Hydrolases, Protons, Macrophage Colony-Stimulating Factor
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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