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Investigations of bones of transgenic mice over expressing human human osteob stimulating factor-1 (OSF-1).

对过度表达人骨刺激因子-1 (OSF-1) 的转基因小鼠骨骼的研究。

基本信息

批准号：
11671447
负责人：
HASHIMOTO-GOTOH Tamotsu
金额：
$ 1.98万
依托单位：
KYOTO Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671447/
关键词：
Osteoblasts osteoporosis OSF1 bone トランスジェニック

项目摘要

We have isolated osteoblast stimulating factor-1 (osf-1), that expressed in osteoblasts, and made transgenic mice over expressing osf-1 to investigate the effect to isotopic osteogenesis. Osf-1 over-expressing transgenic mice increased in bone mineral content, bone mineral density, and bone strength than wild type mice. Ovariectomized osf-1 over expressing mice, which are model of osteoporosis caused by estrogen deficiency, kept as the same bone volume as the sham operated wild type mice.Mating male mice expressing homozyous osf-1, with wild type female mice, we got osf-1 heterozygous littermates. Next, we mated the heterozygous male and the heterozygous female littermates, and got another littermates which had osf-1 gene or not. We used 108 female littermates to examine the bone strength. 14-week-old mice were operated, half number of them were ovariectomized and another half number of them were sham-operated. As a result, we gained 42 mice having transgene and ovariectomized, 11 mice having no transgene and ovariectomized, 46 mice having transgene and sham-operated, 9 mice being negative with transgene and sham-operated. We excised femora of these mice at the age of 28-week-old, and evaluated their failure load of whole femora by three point bending test. The span between the supprts was 9 mm long, and the cross-head-speed was 0.5 mm/min.In sham-operated mice groups, comparing with the transgenic mice and the wild type mice, by the value of failure load/body weight^2/3, the value of the transgenic mice tend to be stronger than that of the wild ones. (p=0.2175) Failure load per unit cross was approximated by that per body weight^2/3.We can suggest the posibility that osf-1 over expression transgenic mice with increasing bone volume are also increasing their bone strength.

我们分离了在成骨细胞中表达的成骨细胞刺激因子-1 (osf-1)，并构建过表达osf-1的转基因小鼠，研究其对同位素成骨的影响。Osf-1过表达转基因小鼠骨矿物质含量、骨矿物质密度和骨强度均高于野生型小鼠。去卵巢osf-1过表达小鼠作为雌激素缺乏所致骨质疏松模型，其骨体积与假手术野生型小鼠相同。表达osf-1纯合子的雄鼠与野生型雌鼠交配，得到osf-1杂合子的仔鼠。然后，我们将杂合的雄性和杂合的雌性交配，得到另一个携带或不携带osf-1基因的幼崽。我们使用了108只雌窝来检查骨骼强度。对14周龄小鼠进行手术，其中一半切除卵巢，另一半假手术。结果得到转基因去卵巢小鼠42只，未转基因去卵巢小鼠11只，转基因假手术小鼠46只，转基因假手术阴性小鼠9只。我们在28周龄时切除这些小鼠的股骨，并通过三点弯曲试验评估其整个股骨的破坏负荷。支座之间的跨度为9mm，交叉速度为0.5 mm/min。在假手术小鼠组中，与转基因小鼠和野生型小鼠相比，在失效负荷/体重^2/3值上，转基因小鼠的失效负荷比野生型小鼠更强。（p=0.2175）每单位交叉的失效载荷近似为每体重的2/3。我们可以推测osf-1过表达转基因小鼠骨体积增加的同时骨强度也增加的可能性。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hashimoto-Gotoh T, Yamaguchi M, Yasojima K, Tsujimura A, Wakabayashi Y., Watanabe Y: "A set of temperature sensitive-replication/-segregation and temperature resistant plasmid vectors with different copy numbers and in an isogenic background"Gene. 241. (2

Hashimoto-Gotoh T、Yamaguchi M、Yasojima K、Tsujimura A、Wakabayashi Y.、Watanabe Y：“一组具有不同拷贝数和等基因背景的温度敏感复制/分离和耐温质粒载体”基因。

DOI：
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Tamotsu Hashimoto Gotoh.et al: "A set of temperature sensitive-replication/-segregation and temperature resistant plasmid vectors with different copy"GENE. 241. 185-191 (2000)

Tamotsu Hashimoto Gotoh.et al：“一组具有不同拷贝的温度敏感复制/分离和耐温质粒载体”GENE。

DOI：
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橋本保,増田治史,山口美樹,辻村敦,中村利孝,平澤泰介,中川雅夫他3名: "ヒト骨芽細胞刺激因子(h-OSF1)による骨粗鬆症遺伝子治療の可能性"オステオポローシスジャパン. 9巻2号(印刷中). (2001)

Tamotsu Hashimoto、Osamu Masuda、Miki Yamaguchi、Atsushi Tsujimura、Toshitaka Nakamura、Taisuke Hirasawa、Masao Nakakawa 和其他 3 人：“使用人成骨细胞刺激因子 (h-OSF1) 进行骨质疏松症基因治疗的可能性”Osteoporosis Japan 第 9 卷第 2 期（正在出版）（2001）。