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Expression of OCZF directed by the cathepsin K promoter affects bone mass and osteoclast formation in Transgenic Mice.

组织蛋白酶 K 启动子指导的 OCZF 表达影响转基因小鼠的骨量和破骨细胞形成。

基本信息

批准号：
17591941
负责人：
KUKITA Akiko
金额：
$ 2.24万
依托单位：
Saga University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591941/
关键词：
osteoclast transcriptional factor transgenic mouse 転写制御因子カテプシンK

项目摘要

The OCZF gene product is a member of POK protein family that contains two domains of POZ/BTB and zinc finger in their N-and C-terminal region respectively, and that is shown to be involved in various cellular processes. Suppression of OCZF by antisense RNA inhibits osteoclast differentiation in vitro, indicating that OCZF is involved in osteoclastogenesis, but in vivo role in the process is not clear. To this end we generated transgenic mice, which expressed OCZF under the control of mouse cathepsin K promoter (Ctsk-OCZF). Nine transgenic mice were identified among the offspring by PCR and Southern blot analysis of mouse tail genomic DNA. Transgene expression was verified by RT-PCR using osteoclasts differentiated in vitro from bone marrow at 10 weeks of age. Two lines of the transgenic animals exhibited relatively high transgene expression, and were further investigated. Micro-CT and peripheral quantitative CT (pQCT) analyses and histomorphometry of femur were performed in mice at 6 weeks of age. Micro-CT imaging demonstrates a reduction in trabecular bone volume in the transgenic mice relative to normal littermates. pQCT analyses also demonstrate a reduction in bone mineral density and bone mineral content especially in trabecular bone with a decrease in strength strain index, whereas those in cortical bone were slightly affected. Consistently, von Kossa staining shows a smaller mineralized area in the transgenic mice than in normal littermates. Histological analyses with tartrate-resistant acid phosphatase staining and calcein labeling indicate an increase in the number of osteoclast, whereas bone formation rate did not significantly change. These data suggest that OCZF/LRF has an important role in osteoclastogenesis in vivo.

OCZF基因产物是POK蛋白家族的一员，在其N端和C端分别含有POZ/BTB和锌指结构域，参与多种细胞过程。反义RNA抑制OCZF在体外抑制破骨细胞的分化，表明OCZF参与破骨细胞的形成，但在体内的过程中的作用还不清楚。为此，我们产生了转基因小鼠，表达OCZF的小鼠组织蛋白酶K启动子（Ctsk-OCZF）的控制下。通过对小鼠尾部基因组DNA的PCR和Southern印迹分析，在后代中鉴定出9只转基因小鼠。使用10周龄时从骨髓中体外分化的破骨细胞通过RT-PCR验证转基因表达。转基因动物的两个品系表现出相对高的转基因表达，并进行了进一步的研究。在6周龄的小鼠中进行股骨的Micro-CT和外周定量CT（pQCT）分析和组织形态计量学。显微CT成像显示，相对于正常同窝出生的小鼠，转基因小鼠的骨小梁体积减少。pQCT分析还表明骨矿物质密度和骨矿物质含量降低，尤其是在骨小梁中，强度应变指数降低，而皮质骨中的骨矿物质密度和骨矿物质含量受到轻微影响。一致地，von Kossa染色显示转基因小鼠中的矿化区域比正常同窝小鼠中的矿化区域小。抗酒石酸酸性磷酸酶染色和钙黄绿素标记的组织学分析表明破骨细胞数量增加，而骨形成率没有显着变化。这些数据表明OCZF/LRF在体内破骨细胞生成中具有重要作用。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

マンネンタケ(Genoderma lucidum)エタノール抽出物による骨粗鬆症予防効果

灵芝乙醇提取物的骨质疏松预防作用

DOI：
发表时间：
2006
期刊：
機能性食品と薬理栄養日本機能性食品医用学会誌 4(1)
影响因子：
0
作者：
T.;Sakae;et. al.;Yamaguchi N;Makoto Sugita;Fukuda T;Makoto Sugita;Fukuda T.;Yamaguchi N.;Makoto Sugita;Tang QY;Ogino Y;清水邦義
通讯作者：
清水邦義

The contribution of platelet-derived growth factor, transforming growth factor-<beta>1 and insulin-like growth factor-1 in platelet-rich plasma (PRP) to the proliferation of osteoclast- like cells

富血小板血浆（PRP）中血小板源性生长因子、转化生长因子-β1和胰岛素样生长因子-1对破骨细胞样细胞增殖的贡献

DOI：
发表时间：
2006
期刊：
Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 101
影响因子：
0
作者：
Ishizuka Y;Moriwaki S;Kawahara-H M;Uemura Y;Serizawa S;Miyauchi M;Shibata S;Kanaya T;Takata T;Taniguchi N;Niida S;Ogino Y.
通讯作者：
Ogino Y.

Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds : succesful suppression of bone destruction accompanied with adjuvant-induced arthritis in rats.

由咖啡酸和相关化合物组成的西蒙提取物对破骨细胞生成的调节：成功抑制大鼠佐剂诱导的关节炎的骨质破坏。

DOI：
发表时间：
2006
期刊：
Histochem Cell Biol. 125(3)
影响因子：
0
作者：
T.;Sakae;et. al.;Yamaguchi N;Makoto Sugita;Fukuda T;Makoto Sugita;Fukuda T.;Yamaguchi N.;Makoto Sugita;Tang QY
通讯作者：
Tang QY

Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds : successful suppression of bone destruction accompanied with adjuvant-induced arthritis in rats.

由咖啡酸和相关化合物组成的西蒙提取物对破骨细胞生成的调节：成功抑制大鼠佐剂诱导的关节炎的骨质破坏。