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诱导的生态骨形成受损。在G-CSF小鼠中，在生态骨形成的早期阶段，间充质细胞的诱导和软骨发生减少。层状结构不成熟，植入BMP-2后3周后，G-CSF小鼠的生态骨中的钙含量得到改善。 G-CSF小鼠及其同窝对照组中，I型 - 胶原蛋白，骨桥蛋白和骨钙素的mRNA表达水平没有显着差异。然而，在G-CSF小鼠中，骨钙素蛋白在雌激素基质中的表达与窝窝小鼠的表达少。将小鼠喂入含有0.05mg MK-4/100G或20.0mg MK-4/100G的小鼠，分别为对照和实验饮食，分别为十二周。这种治疗不会改变骨长度，而与小鼠或饮食类型无关。外围定量计算机断层扫描（PQCT）显示，在MK-4处理的小鼠中骨骼中的CT值增加。（3）我们使用EX-VIVO细胞培养系统研究了G-CSF小鼠骨骼中的细胞和分子异常。在这里，我们证明了转基因小鼠骨髓中的成骨细胞祖细胞的数量减少，但具有支持骨细胞创造的能力。转基因小鼠中酿造以含有破骨细胞祖细胞的骨髓细胞中的CFU-GM显着增加。此外，在转基因小鼠的成骨细胞中，核因子-κB配体的受体激活剂（rank配体； RANKL）的表达相当降低。