Development of high-throughput screening system for osteogenic drugs using a cell-based sensor

被引：17

作者：

Hojo, Hironori ^{[1
,2
]}

Igawa, Kazuyo ^{[1
,3
]}

Ohba, Shinsuke ^{[1
,3
]}

Yano, Fumiko ^{[1
,3
]}

Nakajima, Keiji ^{[1
,3
]}

Komiyama, Yuske ^{[1
,3
]}

Ikeda, Toshiyuki ^{[3
]}

Lichtler, Alexander C. ^{[4
,5
]}

Woo, Je-Tae ^{[6
]}

Yonezawa, Takayuki ^{[6
]}

Takato, Tsuyoshi ^{[3
]}

Chung, Ung-il ^{[1
]}

机构：

[1] Univ Tokyo, Fac Med, Ctr Dis Biol & Integrat Med, Bunkyo Ku, Tokyo 1130033, Japan

[2] Japan Soc Promot Sci, Chiyoda Ku, Tokyo 1028472, Japan

[3] Univ Tokyo, Fac Med, Dept Sensory & Motor Syst Med, Bunkyo Ku, Tokyo 1130033, Japan

[4] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT USA

[5] Univ Connecticut, Ctr Hlth, Dept Orthoped, Farmington, CT USA

[6] Univ Tokyo, Fac Med, Dept Nutriprote, Bunkyo Ku, Tokyo 1130033, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 376卷 / 02期

关键词：

Screening system; Col1a1GFP-MC3T3E1; Small compounds; Osteoblast;

D O I：

10.1016/j.bbrc.2008.08.167

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To effectively treat osteoporosis and other bone-loss disorders, small compounds that potently induce bone formation are needed. The present study initially attempted to establish a monitoring system that Could detect osteogenic differentiation easily, precisely, and noninvasively. For this purpose, we established pre-osteoblastic MC3T3E1 cells stably transfected with the GFP reporter gene driven by a 2.3 kb fragment of rat type I collagen promoter (Col1a1GFP-MC3T3E1). Among these cells, we selected a clone that fluoresced upon osteogenic stimulation by BMP2. The GFP fluorescence intensity corresponded well to the intensity of alkaline phosphatase (ALP) staining and to the level of osteocalcin (Oc) mRNA. Using this system, we screened natural and synthetic compound libraries and thus identified an isoflavone derivative, glabrisoflavone (GI). GI induced ALP staining and Oc mRNA in a dose-dependent manner. The Col1a1GFP-MC3T3E1 system may be useful for identifying novel osteogenic drugs. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：375 / 379

页数：5

共 25 条

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