Study on the effect of colony stimulating factor on bone metabolism

集落刺激因子对骨代谢影响的研究

基本信息

批准号：
10671371
负责人：
WADA Takuro
金额：
$ 1.98万
依托单位：
Sapporo Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671371/
关键词：
G-CSF osteoporosis transgenic mice osteoclasts osteoblasts BMP-2 Toll-like receptor lung adenocarcinoma 骨量骨形成 Bone morphogenic protein

项目摘要

(1) We have shown that ectopic bone formation induced by BMP-2 was impaired in transgenic mice overproducing G-CSF. In G-CSF mice, induction of mesenchymal cells and chondrogenesis diminished at early stage of ectopic bone formation. The lamellar structure was immature and the calcium content was decreased in the ectopic bone of G-CSF mice 3 weeks after the implantation of BMP-2. There was no significant difference in mRNA expression levels of type I-collagen, osteopontin, and osteocalcin in the ectopic bone among G-CSF mice and their littermate controls. However, the expression of osteocalcin protein in the ectopic bone matrix was less in G-CSF mice than that in littermates.(2) The effect of vitamin K2 (menatetrenone) (MK4) on bone phenotypes during development was examined. Mice were fed chow k containing either 0.05mg MK-4/100g or 20.0mg MK-4/100g for twelve weeks as the control and experimental diets, respectively.This treatment did not change bone length, irrespective of the type of mice or diet. Peripheral quantitative computed tomography(pQCT)revealed an increase of the CT value in bone in MK-4 treated mice.(3) We investigated the cellular and molecular abnormality in the bone of G-CSF mice using ex-vivo cell culture system. Here we demonstrate that osteoblast progenitors in bone marrow oftransgenic mice are diminished in number but possess increased ability to support osteoclastgenesis. CFU-GM in bone marrow cells, which is blieved to contain osteoclast progenitors, was significantly increased in transgenic mice. In addition, the expression of receptor activator of nuclear factor- κ B ligand (RANK ligand ; RANKL) was rather decreased in osteoblasts oftransgenic mice.

(1)我们已经表明，在过量产生G-CSF的转基因小鼠中，BMP-2诱导的异位骨形成受到损害。在G-CSF小鼠中，间充质细胞和软骨形成的诱导在异位骨形成的早期阶段减弱。植入BMP-2后3周,G-CSF小鼠异位骨中钙含量未成熟且钙含量下降,各型mRNA表达水平无显着差异。 G-CSF小鼠及其同窝小鼠异位骨中的I-胶原、骨桥蛋白和骨钙素的表达，但G-CSF小鼠异位骨基质中骨钙素蛋白的表达较同窝小鼠少。(2)研究人员检查了维生素 K2（甲那曲酮）（MK4）对发育过程中骨表型的影响，给小鼠喂食含有 0.05 毫克 MK-4/100 克或 0.05 毫克 MK-4 的饲料。 20.0mg MK-4/100g 分别作为对照和实验饮食，持续十二周。无论小鼠类型或饮食如何，这种治疗都不会改变骨长度。外周定量计算机断层扫描（pQCT）显示 CT 值增加。 (3)我们利用离体细胞培养系统研究了G-CSF小鼠骨骼中的细胞和分子异常。转基因小鼠骨髓中的祖细胞数量减少，但支持骨髓细胞中的CFU-GM（据信含有破骨细胞祖细胞）的能力显着增加。此外，受体激活剂的表达显着增加。转基因小鼠成骨细胞中核因子-κB配体（RANK配体；RANKL）的表达明显减少。