Cited by 693Bone Metabolism and DiseasesRheumatoid Arthritis Research and TherapiesOsteomyelitis and Bone Disorders Research

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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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Arai, Fumio, Miyamoto, Takeshi, Ohneda, Osamu, Inada, Tomohisa, Sudo, Tetsuo, Brasel, Kenneth, Miyata, Takashi, Anderson, Dirk M., Suda, Toshio·1999·The Journal of Experimental Medicine

DOI 10.1084/jem.190.12.1741PMC PMC2195707

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Abstract

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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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
ORCID: Arai, Fumio
Miyamoto, Takeshi
Ohneda, Osamu
Miyata, Takashi
Anderson, Dirk M.
Suda, Toshio
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
DOI: 10.1084/jem.190.12.1741
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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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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