Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor κB (RANK) receptors.
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Osteoclasts are terminally differentiated cells derived from hematopoietic stem cells. However, how their precursor cells diverge from macrophagic lineages is not known. We have identified early and late stages of osteoclastogenesis, in which precursor cells sequentially express c-Fms followed by receptor activator of nuclear factor κB (RANK), and have demonstrated that RANK expression in early-stage of precursor cells (c-Fms+RANK−) was stimulated by macrophage colony-stimulating factor (M-CSF). Although M-CSF and RANKL (ligand) induced commitment of late-stage precursor cells (c-Fms+RANK+) into osteoclasts, even late-stage precursors have the potential to differentiate into macrophages without RANKL. Pretreatment of precursors with M-CSF and delayed addition of RANKL showed that timing of RANK expression and subsequent binding of RANKL are critical for osteoclastogenesis. Thus, the RANK–RANKL system determines the osteoclast differentiation of bipotential precursors in the default pathway of macrophagic differentiation.
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Glucocorticoids stimulate osteoblasts to produce M-CSF, an important cofactor for osteoclastogenesis.
“Glucocorticoids also stimulate osteoblasts to produce M-CSF (260), which is an important cofactor for osteoclastogenesis (261).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [261]
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- Authors
- Arai, F., Miyamoto, T., Ohneda, O., Inada, T., Sudo, T., Brasel, K., Miyata, T., Anderson, D. M., & Suda, T.
- Affiliations
- Meikai University (JP)
- Institute of Molecular Embryology and Genetics, Kumamoto University (JP)
- Toray Industries, Inc. (Japan) (JP)
- dDepartment of Molecular Biology, Immunex Corporation, Seattle, Washington 98101-2936
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1999-12-20
- Volume
- 190
- Issue
- 12
- Pages
- 1741-1754
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2195707
- OpenAlex
- W2132408993
- Cited by
- 693
- References
- 54
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 20 · 2023: 33 · 2022: 33 · 2021: 32 · 2020: 42 · 2019: 38 · 2018: 31 · 2017: 31 · 2016: 30 · 2015: 40 · 2014: 34 · 2013: 31 · 2012: 38
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Keywords
- osteoclastogenesis, osteoclast precursor cells, c-fms, RANK, RANKL, macrophage colony-stimulating factor, macrophage differentiation, lineage commitment, hematopoietic stem cells
- MeSH terms
- Animals, Carrier Proteins, Cell Differentiation, Hematopoietic Stem Cells, Ligands, Macrophages, Membrane Glycoproteins, Mice, Inbred C57BL, Osteoclasts, Macrophage Colony-Stimulating Factor, Receptor, Macrophage Colony-Stimulating Factor, Receptors, Tumor Necrosis Factor, Cell Lineage, Mice, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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