Identification of genes induced by mechanical stress in osteocytes
骨细胞机械应力诱导基因的鉴定
基本信息
- 批准号:13671947
- 负责人:
- 金额:$ 2.05万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2001
- 资助国家:日本
- 起止时间:2001 至 2002
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The mechanical stress is one of important factor to prevent osteoporosis and is considered to control bone resorption and formation. Osteocytes are most abundant cells in bone, and seem to more responsive to the mechanical stress than osteoblast or osteoclast. We investigated the genes relating to mechanical stress to reveal a role of mechanical stress in osteocytes.1. We identified cis-acting elements and trans-acting factors on 5' flanking regions of cyclooxygenase-2 gene stimulated by mechanical stress in MLO-Y4-A2 cells. NF-IL6, CREB, API were identified as trans-acting factors which bound to cis-acting elements of 5' flanking regions of cyclooxygenase-2 gene and induced cyclooxygenase-2 mRNA. These factors should be used as markers exploring machano-sensor of mechanical stress on plasma membrane of cells. (preparing for publication)2. We investigated the induction of parathyroid hormone (PTH) receptor by fluid shear stress in MLO-Y4-A2 osteocyte-like cells. When the fluid shear stress was exposed to MLO-Y4-A2 cells, PTH receptor mRNA was increased by about 6.2 times at 7 h analyzed by RT-PCR. Lusiferase assay with the promoter/enhancer domain considered the transcriptional regulation of PTH receptor by stress loading. The deletion analysis of promoter/enhancer domain revealed that the domain containing P1 region was correlated to the induction of PTH receptor. The fluid shear stress phosphorylated ERK-1 which was an up-stream signaling of COX-2 induction. However, PTH receptor induction was not inhibited by U-0126, ERK kinase inhibitor. These results suggested that the fluid shear stress was induced PTH receptor under transcriptional controls through a different signaling pathway from ERK/COX-2/PGE2. (preparing for publication)3. We identified other genes induced by mechanical stress, such as estrogen receptor α, CD44 antigen, ODF. We also identified some unidentified genes in MLO-Y4-A2 osteocyte-like cells. We have continued to analyzed these genes
机械应力是预防骨质疏松症的重要因素之一,被认为控制骨吸收和骨形成。骨细胞是骨中最丰富的细胞,似乎比成骨细胞和破骨细胞对机械应力更敏感。我们研究了与机械应力相关的基因,以揭示机械应力在骨细胞中的作用。我们在MLO-Y4-A2细胞中发现了机械应力刺激下环氧化酶-2基因5'侧的顺式作用元件和反式作用因子。NF-IL6、CREB、API是结合环氧化酶-2基因5′侧区顺式作用元件并诱导环氧化酶-2 mRNA的反式作用因子。这些因素可作为探索细胞质膜机械应力传感器的标记物。(准备出版)我们研究了液体剪切应力对MLO-Y4-A2骨细胞样细胞甲状旁腺激素受体的诱导作用。当流体剪切应力作用于MLO-Y4-A2细胞时,RT-PCR分析PTH受体mRNA在7 h时升高约6.2倍。启动子/增强子区域的荧光素酶分析考虑了PTH受体在应激负荷下的转录调控。启动子/增强子结构域的缺失分析表明含有P1区域的结构域与PTH受体的诱导有关。流体剪切应力使ERK-1磷酸化,这是COX-2诱导的上游信号。而ERK激酶抑制剂U-0126未抑制PTH受体的诱导。这些结果表明,在转录控制下,流体剪切应力通过与ERK/COX-2/PGE2不同的信号通路诱导PTH受体。(准备出版)我们还鉴定了机械应力诱导的其他基因,如雌激素受体α、CD44抗原、ODF。我们还在MLO-Y4-A2骨细胞样细胞中发现了一些未识别的基因。我们继续分析这些基因
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ARAKAWA Toshiya其他文献
ARAKAWA Toshiya的其他文献
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{{ truncateString('ARAKAWA Toshiya', 18)}}的其他基金
Analysis of a crosstalk signaling between mechanical stress and lyso-phospholipid signals in periodontal ligament
牙周膜机械应力和溶血磷脂信号之间的串扰信号分析
- 批准号:
22592074 - 财政年份:2010
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Effect of mechanical stress on osteogenesis facilitating by parathyroid hormone
机械应力对甲状旁腺激素促进成骨的影响
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15591974 - 财政年份:2003
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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