論文 - 詳細
| RRC ID | 19238 |
|---|---|
| 著者 | Kido S, Kuriwaka-Kido R, Umino-Miyatani Y, Endo I, Inoue D, Taniguchi H, Inoue Y, Imamura T, Matsumoto T. |
| タイトル | Mechanical stress activates Smad pathway through PKCδ to enhance interleukin-11 gene transcription in osteoblasts. |
| ジャーナル | PLoS One |
| Abstract |
BACKGROUND:Mechanical stress rapidly induces ΔFosB expression in osteoblasts, which binds to interleukin (IL)-11 gene promoter to enhance IL-11 expression, and IL-11 enhances osteoblast differentiation. Because bone morphogenetic proteins (BMPs) also stimulate IL-11 expression in osteoblasts, there is a possibility that BMP-Smad signaling is involved in the enhancement of osteoblast differentiation by mechanical stress. The present study was undertaken to clarify whether mechanical stress affects BMP-Smad signaling, and if so, to elucidate the role of Smad signaling in mechanical stress-induced enhancement of IL-11 gene transcription. METHODOLOGY/PRINCIPAL FINDINGS:Mechanical loading by fluid shear stress (FSS) induced phosphorylation of BMP-specific receptor-regulated Smads (BR-Smads), Smad1/5, in murine primary osteoblasts (mPOBs). FSS rapidly phosphorylated Y311 of protein kinase C (PKC)δ, and phosphorylated PKCδ interacted with BR-Smads to phosphorylate BR-Smads. Transfection of PKCδ siRNA or Y311F mutant PKCδ abrogated BR-Smads phosphorylation and suppressed IL-11 gene transcription enhanced by FSS. Activated BR-Smads bound to the Smad-binding element (SBE) of IL-11 gene promoter and formed complex with ΔFosB/JunD heterodimer via binding to the C-terminal region of JunD. Site-directed mutagenesis in the SBE and the AP-1 site revealed that both SBE and AP-1 sites were required for full activation of IL-11 gene promoter by FSS. CONCLUSIONS/SIGNIFICANCE:These results demonstrate that PKCδ-BR-Smads pathway plays an important role in the intracellular signaling in response to mechanical stress, and that a cross-talk between PKCδ-BR-Smads and ΔFosB/JunD pathways synergistically stimulates IL-11 gene transcription in response to mechanical stress. |
| 巻・号 | 5(9) |
| 公開日 | 2010-9-29 |
| DOI | 10.1371/journal.pone.0013090 |
| PII | e13090 |
| PMID | 20927330 |
| PMC | PMC2947522 |
| MeSH | Animals Bone Morphogenetic Proteins / genetics Bone Morphogenetic Proteins / metabolism Cell Line Cells, Cultured Humans Interleukin-11 / genetics* Interleukin-11 / metabolism Mice Osteoblasts / chemistry* Osteoblasts / enzymology Osteoblasts / metabolism* Phosphorylation Protein Binding Protein Kinase C-delta / genetics Protein Kinase C-delta / metabolism* Signal Transduction* Smad Proteins / genetics Smad Proteins / metabolism* Stress, Mechanical Transcription, Genetic* |
| IF | 2.74 |
| 引用数 | 33 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |