Cited by 442Bone Metabolism and DiseasesSignaling Pathways in DiseaseNuclear Receptors and Signaling

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The Role of NFAT in Osteoclast Formation

TAKAYANAGI, HIROSHI·2007·Annals of the New York Academy of Sciences

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Abstract

Osteoclasts are cells of monocyte-macrophage origin that degrade bone matrix. Receptor activator of NF-kappaB ligand (RANKL) induces osteoclast formation in the presence of macrophage-colony-stimulating factor (M-CSF) and costimulatory signals. RANKL induces activation of the TNF receptor-associated factor 6 (TRAF6) and c-Fos pathways, which lead to the osteoclast-specific event, that is, autoamplification of nuclear factor of activated T cells (NFAT)c1, the master transcription factor for osteoclast differentiation. Autoamplification of NFATc1 is dependent on the calcium signaling of immunoglobulin-like receptors associated with immunoreceptor tyrosine-based activation motif (ITAM)-harboring adaptors. In addition to the calcineurin-NFATc1 axis, calcium signaling activates the calmodulin-dependent kinase pathway, which also plays a critical role in osteoclast formation. Such advances in the understanding of the molecular mechanism of osteoclast differentiation are expected to lead to novel therapeutic approaches to bone diseases.

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Authors: TAKAYANAGI, H.
Affiliations: Tokyo Medical and Dental University (JP)
Corresponding author: TAKAYANAGI, HIROSHI
ORCID: TAKAYANAGI, HIROSHI
Venue: Annals of the New York Academy of Sciences
Publisher: Wiley
Published: 2007-11
Volume: 1116
Issue: 1
Pages: 227-237
ISSN: 0077-8923 (ISSN-L)
1749-6632
DOI: 10.1196/annals.1402.071
OpenAlex: W1975505424
Cited by: 442
References: 36
Citations by year: 2026: 6 · 2025: 16 · 2024: 16 · 2023: 21 · 2022: 23 · 2021: 21 · 2020: 33 · 2019: 35 · 2018: 34 · 2017: 28 · 2016: 31 · 2015: 38 · 2014: 19 · 2013: 22 · 2012: 29
FWCI: 1.13
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 42 d)
Locations: Annals of the New York Academy of Sciences (publishedVersion)
PubMed (publishedVersion)
Funders: Kanae Foundation for the Promotion of Medical Science
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords: osteoclastogenesis, NFATc1, RANKL, TRAF6, c-fos, calcineurin, calcium signaling, calcium/calmodulin-dependent protein kinase, ITAM, macrophage colony-stimulating factor, bone resorption, bone disease
MeSH terms: Animals, Humans, Osteoclasts, Transcription, Genetic, Signal Transduction, NFATC Transcription Factors, RANK Ligand

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The Role of NFAT in Osteoclast Formation

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