Reference - Detail
| RRC ID | 51749 |
|---|---|
| Author | Zhang Q, Matsui H, Horiuchi H, Liang X, Sasaki K. |
| Title | A-Raf and C-Raf differentially regulate mechanobiological response of osteoblasts to guide mechanical stress-induced differentiation. |
| Journal | Biochem Biophys Res Commun |
| Abstract |
Regulation of osteoblast activity by mechanical stress is important for bone remodeling. However, the precise mechanotransduction mechanism that triggers the anabolic reaction of osteoblasts is largely unknown. In this study, we performed RNA interference (RNAi) screening to identify the signaling molecules upstream of ERK, which was responsible for osteogenesis. Of twenty-two mitogen-activated protein kinase (MAPK) kinase kinases (MAP3Ks), we identified A-Raf and C-Raf as upstream MAP3Ks of the mechanical stretch-activated ERK pathway. Subsequently we screened the mechanosensitive cation channel, and identified P2X7 as an upstream molecule of the ERK pathway. Intriguingly, P2X7 functioned as an upstream activator of A-Raf but not of C-Raf. Furthermore, A-Raf contributed to mechanical stretch-induced osteoblast differentiation. In contrast, C-Raf but not A-Raf protected osteoblasts from mechanical stretch-induced apoptosis. These results suggested that A-Raf and C-Raf were involved in mechanobiological osteogenesis in a distinct way: A-Raf was responsible for osteogenesis while C-Raf for anti-apoptotic protection and promotion. |
| Volume | 476(4) |
| Pages | 438-444 |
| Published | 2016-8-5 |
| DOI | 10.1016/j.bbrc.2016.05.141 |
| PII | S0006-291X(16)30863-4 |
| PMID | 27240957 |
| MeSH | Animals Cell Differentiation / physiology Cell Line Cell Survival MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism Mice Mitogen-Activated Protein Kinases / genetics Mitogen-Activated Protein Kinases / metabolism Osteoblasts / cytology* Osteoblasts / physiology Proto-Oncogene Proteins A-raf / genetics Proto-Oncogene Proteins A-raf / metabolism* Proto-Oncogene Proteins c-raf / genetics Proto-Oncogene Proteins c-raf / metabolism* RNA Interference Receptors, Purinergic P2X7 / genetics Receptors, Purinergic P2X7 / metabolism Stress, Mechanical |
| IF | 2.985 |
| Times Cited | 4 |
| Altmetric score |
オルトメトリクス指標項目
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| 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 | MC3T3-E1(RCB1126) |