Cited by 380Bone Metabolism and DiseasesSignaling Pathways in DiseaseBone and Dental Protein Studies

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Large Scale Gene Expression Analysis of Osteoclastogenesisin Vitro and Elucidation of NFAT2 as a Key Regulator

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Ishida, Norihiro, Hayashi, Koji, Hoshijima, Mitsuhiro, Ogawa, Takuya, Koga, Shintaro, Miyatake, Yuuki, Kumegawa, Masayoshi, Kimura, Toru, Takeya, Tatsuo·2002·Journal of Biological Chemistry

DOI 10.1074/jbc.m205063200

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Abstract

To understand the molecular events coupling between cell proliferation and differentiation by elucidating genes essential for the process, we conducted a large scale gene expression analysis of an in vitro osteoclastogenesis system consisting of recombinant RANKL and mouse RAW264 cells. The entire process leading to the formation of tartrate resistant acid phosphatase-positive multinucleated cells takes 3 days and plates become fully covered with multinucleated cells at 4 days. Microarray probing at eight time points revealed 635 genes that showed greater than 2-fold differential expression for at least one time point and they could be classified into six groups by the "k-means" clustering analysis. Among a group of 106 early inducible genes (within 2-5 h after RANKL stimulation), four genes including NFAT2 were identified as genes whose enhanced expressions were fairly correlated with an efficient induction of matured osteoclasts. Moreover, cyclosporin A significantly suppressed the multinucleated cell formation accompanying the reduction of the nuclear localization of NFAT2. When the expression of NFAT2 was suppressed by introducing antisense NFAT2, multinucleated cell formation was severely hampered. Functional analysis thus combined with gene analysis by microarray technology elucidated a key role of NFAT2 in osteoclastogenesis in vitro.

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Self-citation
Fibrillin-1 directly regulates osteoclast formation and function by a dual mechanism
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Authors: Ishida, N., Hayashi, K., Hoshijima, M., Ogawa, T., Koga, S., Miyatake, Y., Kumegawa, M., Kimura, T., & Takeya, T.
Affiliations: Nara Institute of Science and Technology (JP)
Meikai University (JP)
Corresponding author: Takeya, Tatsuo
ORCID: Hoshijima, Mitsuhiro
Ogawa, Takuya
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2002-10
Volume: 277
Issue: 43
Pages: 41147-41156
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m205063200
OpenAlex: W2067233675
Cited by: 377
References: 63
Citations by year: 2026: 3 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 13 · 2021: 12 · 2020: 7 · 2019: 14 · 2018: 15 · 2017: 11 · 2016: 8 · 2015: 15 · 2014: 22 · 2013: 13 · 2012: 30
FWCI: 6.97
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6589 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
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 › Biochemistry › Bone and Dental Protein Studies
Keywords: osteoclastogenesis, NFATc1, RANKL, RAW264 cells, gene expression profiling, cyclosporine, tartrate-resistant acid phosphatase, transcriptional regulation, cell differentiation, antisense RNA knockdown
MeSH terms: Animals, Base Sequence, Carrier Proteins, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Glutathione Transferase, Imidazoles, Membrane Glycoproteins, Nuclear Proteins, Osteoclasts, Pyridines, Subcellular Fractions, Transcription Factors, Cyclosporine, DNA Primers, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, NFATC Transcription Factors, Mice, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

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Large Scale Gene Expression Analysis of Osteoclastogenesisin Vitro and Elucidation of NFAT2 as a Key Regulator

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