Analysis of the role of mechanosensor-mediated JNK/p38 signaling in osteoimmunological regulation of osteoblasts

机械传感器介导的 JNK/p38 信号在成骨细胞骨免疫调节中的作用分析

• 批准号: 24792059
• 负责人: MATSUI Hiroyuki
• 金额: $ 2.66万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24792059/
• 关键词: メカノバイオロジー; 骨代謝; JNK; p38; ERK; メカノトランスダクション; ストレス応答MAPキナーゼ; 骨免疫学; メカノバイオロジー; 骨代謝; JNK; p38; ERK; メカノトランスダクション; ストレス応答MAPキナーゼ; 骨免疫学

In this study, we report that large-magnitude (12%) cyclic stretch induced Ca2+ influx in MC3T3-E1 osteoblasts, which subsequently activated ASK1 MAP3K. The activated ASK1-JNK lead to transiently enhanced expression of FGF-inducible 14 (Fn14, a member of the TNF receptor superfamily) gene. Cells with enhanced expression of Fn14 subsequently acquired sensitivity to the ligand of Fn14, TNF-related weak inducer of apoptosis, and underwent apoptosis. On the other hand, ASK1-p38 pathway induced expression of monocyte chemoattractant protein-3 (MCP-3) gene, which promoted chemotaxis of pre-osteoclasts. These results suggest that ASK1-JNK/p38 pathways contribute to the mechanism of mechanical overloading-induced bone resroption via cytokine-related gene expression.

在这项研究中，我们报告说，MC3T3-E1成骨细胞中的大含量（12％）循环诱导的Ca2+涌入，随后激活了ASK1 MAP3K。激活的ask1-jnk导致FGF诱导14（FN14，TNF受体超家族）基因的瞬时增强表达。 FN14表达增强的细胞随后获得了对FN14配体的敏感性，TNF相关的细胞凋亡的弱诱导剂，并经历了凋亡。另一方面，ASK1-P38途径诱导单核细胞趋化剂蛋白-3（MCP-3）基因的表达，该基因促进了前骨前细胞的趋化性。这些结果表明，ASK1-JNK/p38途径通过细胞因子相关基因表达有助于机械超载诱导的骨反应的机理。