Reference - Detail
| RRC ID | 45285 |
|---|---|
| Author | Kanzaki H, Shinohara F, Kajiya M, Fukaya S, Miyamoto Y, Nakamura Y. |
| Title | Nuclear Nrf2 induction by protein transduction attenuates osteoclastogenesis. |
| Journal | 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. |
| Volume | 77 |
| Pages | 239-48 |
| Published | 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 |
| Times Cited | 22 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY ENDOCRINOLOGY & METABOLISM |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | RAW 264(RCB0535) |