The DOI matches its Crossref record; 61 of the 63 references it cites were found in a registry or an index.
Large Scale Gene Expression Analysis of Osteoclastogenesisin Vitro and Elucidation of NFAT2 as a Key Regulator
Open accessAbstract
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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“NFATc1 is a transcription factor that plays a master role in osteoclastogenesis168 by regulating the expression of osteoclast-specific genes such as cathepsin K, DC-STAMP, and tartrate-resistant acid phosphatase (TRAP) or that of osteoclast-associated receptor (OSCAR) and other genes involved in OC resorptive functions.169”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [168]
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Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670
Takayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J.-I., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00369-6 · Cited by 2,701
Transcriptional regulation by calcium, calcineurin, and NFAT
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Teitelbaum, S. L., & Ross, F. P. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1122 · Cited by 1,720
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Metadata
- 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
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 277
- Issue
- 43
- Pages
- 41147-41156
- ISSN
- 0021-9258 (ISSN-L)
- 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
- 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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