Cited by 95Bone Metabolism and DiseasesOsteomyelitis and Bone Disorders ResearchBone health and osteoporosis research

The origins and formation of bone-resorbing osteoclasts

Elson, Ari, Anuj, Anuj, Barnea-Zohar, Maayan, Reuven, Nina·2022·Bone

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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Crossref · 10.1016/j.bone.2022.116538

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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
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

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