論文 - 詳細
| RRC ID | 45285 |
|---|---|
| 著者 | Kanzaki H, Shinohara F, Kajiya M, Fukaya S, Miyamoto Y, Nakamura Y. |
| タイトル | Nuclear Nrf2 induction by protein transduction attenuates osteoclastogenesis. |
| ジャーナル | Free Radic Biol Med |
| Abstract |
It has been reported that reactive oxygen species (ROS) play a role as intracellular signaling molecules in RANKL stimulation. Previously we demonstrated that induction of cytoprotective enzyme expression by Nrf2-gene transfer successfully ameliorated RANKL-dependent osteoclastogenesis. In the present study, we hypothesized that Nrf2 activation by inhibiting ubiquitination and degradation of Nrf2 by ETGE-peptide would induce Nrf2-dependent cytoprotective enzyme expression, attenuate ROS signaling, and thereby inhibit RANKL-dependent osteoclastogenesis. ETGE-peptide containing a cell-permeable sequence (seven consecutive arginine; 7R-ETGE) was applied to a mouse macrophage cell-line RAW 264.7 cell or a primary macrophage culture. ETGE-peptide prevents Keap1 from binding to Nrf2. Nrf2 nuclear translocation and Nrf2-dependent cytoprotective enzyme induction was observed. The effects of 7R-ETGE on RANKL-dependent induction of intracellular ROS levels and osteoclastogenesis were examined. Finally, the protective effect of 7R-ETGE on RANKL-mediated bone destruction was investigated in mice. 7R-ETGE dose-dependently induced nuclear Nrf2, followed by the induction of cytoprotective enzyme expression at both the gene and protein level. 7R-ETGE inhibited upregulation of intracellular ROS levels by RANKL stimulation, and osteoclastogenesis was attenuated. Of particular interest was that local injection of 7R-ETGE ameliorated RANKL-mediated bone destruction. Local induction of nuclear Nrf2 by protein transduction is a potential novel therapeutic target for bone destruction diseases such as periodontitis and rheumatoid arthritis. |
| 巻・号 | 77 |
| ページ | 239-48 |
| 公開日 | 2014-12-1 |
| DOI | 10.1016/j.freeradbiomed.2014.09.006 |
| PII | S0891-5849(14)00425-0 |
| PMID | 25224039 |
| MeSH | Active Transport, Cell Nucleus Animals Bone Density Conservation Agents / pharmacology* Cell Line Cell Nucleus / metabolism* Male Mice, Inbred C57BL NF-E2-Related Factor 2 / metabolism* Oligopeptides / pharmacology* Osteoclasts / drug effects Osteoclasts / physiology* RANK Ligand / pharmacology RANK Ligand / physiology Reactive Oxygen Species / metabolism |
| IF | 6.17 |
| 引用数 | 22 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY ENDOCRINOLOGY & METABOLISM |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |