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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)我们已经证明BMP-2诱导的异位骨形成在过量产生G-CSF的转基因小鼠中受到损害。在G-CSF小鼠中，间充质细胞的诱导和软骨形成在异位骨形成的早期阶段减弱。BMP-2植入3周后，G-CSF小鼠异位骨板层结构不成熟，钙含量降低。G-CSF小鼠异位骨中i型胶原、骨桥蛋白和骨钙素mRNA表达水平与对照组无显著差异。然而，G-CSF小鼠异位骨基质中骨钙素蛋白的表达低于同窝鼠。(2)考察维生素K2 (menattreone) （MK4）对发育期间骨表型的影响。小鼠分别饲喂含有0.05mg MK-4/100g或20.0mg MK-4/100g的chow k作为对照和实验饲料12周。无论老鼠的类型或饮食如何，这种治疗都没有改变骨头的长度。外周定量计算机断层扫描（pQCT）显示MK-4处理小鼠骨的CT值增加。(3)利用离体细胞培养系统研究了G-CSF小鼠骨内的细胞和分子异常。本研究表明，转基因小鼠骨髓中的成骨细胞祖细胞数量减少，但支持破骨细胞发生的能力增强。骨髓细胞被认为含有破骨细胞祖细胞，CFU-GM在转基因小鼠中显著增加。此外，转基因小鼠成骨细胞中核因子- κ B受体激活因子配体（receptor activator of nuclear factor- κ B ligand， RANK配体；RANKL）的表达明显降低。