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Produdion of transgenic mice and functional analysis ofosteaytesusingcis-regulatory regions

转基因小鼠的产生及顺式调控区骨干细胞的功能分析

基本信息

批准号：
17390484
负责人：
TOYOSAWA Satoru
金额：
$ 10.18万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390484/
关键词：
therapy with nucleic acid arthritis osteoarthritis osteosarcoma lung metastasis NFkB E2F transcription factor

项目摘要

Osteocytes are the most abundant cells in bone. There are approximately 10 times as many osteocytes as osteoblasts in mature bone. Previous studies suggested that osteocytes may be involved in mechanosensing and Ca^<2+> metabolism. However, inside of bone is a network of numerous osteocytes, whose specific function has remained an enigma. DMP1 is highly expressed in the osteocyte and therefore a good marker for the osteocyte lineage and is specifically expressed along and in the canaliculi of osteocytes within the bone matrix. The hypothesis is that the cis-regulatory region of the DMP1 gene contains an osteocyte-specific control module that will activate the endogenous DMP1 gene. Therefore, we identified the 12Kbp cis-regulatory region, which contained osteocyte-specific control module. Then, we made the constructs of cis-regulatory regions of DMP1-GFP, to generation of the transgenic mice that express GFP specifically in the osteocyte.Recent study using DMP1-null mice demonstrated that absence of DMP1 results in defective osteocyte maturation and increased FGF23 expression, leading to renal phosphate-wasting associated hypophosphatamia. Based on this result, we hypothesize that DMP1-overexpression will result in decreased FGF23 expression, leading to hyperphosphatemia. Then we evaluate the phosphate homeostasis and serum FGF-23 in DMP1-overexpressed transgenic mice (DMP1-Tg). There is no significance of TmP/GFR and serum FGF23 values between DMP1-Tg and wild mice. Our findings indicated that DMP1 did not directly induced FGF-23 expression in bony tissue and that loss of DMP1 inducing osteomalacia may lead to increased FGF-23 in bony tissue.

骨细胞是骨骼中最丰富的细胞。成熟骨中的骨细胞数量大约是成骨细胞数量的 10 倍。先前的研究表明骨细胞可能参与机械传感和Ca 2+ 代谢。然而，骨骼内部是一个由大量骨细胞组成的网络，其具体功能仍然是个谜。 DMP1 在骨细胞中高度表达，因此是骨细胞谱系的良好标记物，并且沿着骨基质内的骨细胞小管和在骨小管中特异性表达。假设 DMP1 基因的顺式调控区包含骨细胞特异性控制模块，该模块将激活内源性 DMP1 基因。因此，我们鉴定了12Kbp顺式调控区，其中包含骨细胞特异性控制模块。然后，我们构建了 DMP1-GFP 的顺式调控区，以产生在骨细胞中特异性表达 GFP 的转基因小鼠。最近使用 DMP1 缺失小鼠的研究表明，DMP1 的缺失会导致骨细胞成熟缺陷和 FGF23 表达增加，导致肾磷酸盐消耗相关的低磷血症。基于这一结果，我们假设 DMP1 过度表达将导致 FGF23 表达减少，从而导致高磷血症。然后我们评估了 DMP1 过表达转基因小鼠 (DMP1-Tg) 的磷酸盐稳态和血清 FGF-23。 DMP1-Tg 与野生小鼠之间 TmP/GFR 和血清 FGF23 值无显着性。我们的研究结果表明，DMP1 并不直接诱导骨组织中 FGF-23 的表达，诱导骨软化的 DMP1 缺失可能导致骨组织中 FGF-23 增加。

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）

A immunohistochemical study of the peripheral ameloblastoma

DOI：
10.1111/j.1601-0825.2006.01340.x
发表时间：
2007-11-01
期刊：
ORAL DISEASES
影响因子：
3.8
作者：
Kishino, M.;Murakami, S.;Toyosawa, S.
通讯作者：
Toyosawa, S.

Roles of DMP1 in the bone

DMP1 在骨骼中的作用

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Sato S;Kitagawa M;Sakamoto K;Iizuka S;Kudo Y;Ogawa I;Miyauchi M;Foster BL;Somerman MJ;Takata T.;Masae Kitagawa;豊澤悟
通讯作者：
豊澤悟

Identification and characterization of bonesialoprotein genes in reptile and amphibian

爬行动物和两栖动物骨唾液蛋白基因的鉴定和表征