論文 - 詳細
| RRC ID | 41647 |
|---|---|
| 著者 | Ishida N, Hayashi K, Hoshijima M, Ogawa T, Koga S, Miyatake Y, Kumegawa M, Kimura T, Takeya T. |
| タイトル | Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator. |
| ジャーナル | J Biol Chem |
| 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. |
| 巻・号 | 277(43) |
| ページ | 41147-56 |
| 公開日 | 2002-10-25 |
| DOI | 10.1074/jbc.M205063200 |
| PII | S0021-9258(19)72231-5 |
| PMID | 12171919 |
| MeSH | Animals Base Sequence Carrier Proteins / pharmacology Cell Line Cyclosporine / pharmacology DNA Primers DNA-Binding Proteins / metabolism DNA-Binding Proteins / physiology* Gene Expression Profiling* Gene Expression Regulation / drug effects Gene Expression Regulation / physiology* Glutathione Transferase / pharmacology Imidazoles / pharmacology Membrane Glycoproteins / pharmacology Mice NFATC Transcription Factors Nuclear Proteins* Oligonucleotide Array Sequence Analysis Osteoclasts / cytology* Osteoclasts / drug effects Osteoclasts / metabolism Pyridines / pharmacology RANK Ligand Receptor Activator of Nuclear Factor-kappa B Subcellular Fractions / metabolism Transcription Factors / metabolism Transcription Factors / physiology* |
| IF | 4.238 |
| 引用数 | 303 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |