RRC ID 43464
著者 Hojo H, Igawa K, Ohba S, Yano F, Nakajima K, Komiyama Y, Ikeda T, Lichtler AC, Woo JT, Yonezawa T, Takato T, Chung UI.
タイトル Development of high-throughput screening system for osteogenic drugs using a cell-based sensor.
ジャーナル Biochem Biophys Res Commun
Abstract 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.
巻・号 376(2)
ページ 375-9
公開日 2008-11-14
DOI 10.1016/j.bbrc.2008.08.167
PII S0006-291X(08)01725-7
PMID 18789892
MeSH Alkaline Phosphatase / analysis Alkaline Phosphatase / biosynthesis Animals Biosensing Techniques / methods* Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins / pharmacology Cell Line Collagen Type I / genetics Drug Evaluation, Preclinical / methods* Fluorescence Genes, Reporter Green Fluorescent Proteins / analysis Green Fluorescent Proteins / genetics Isoflavones / pharmacology Mice Osteoblasts / drug effects* Osteocalcin / analysis Osteocalcin / biosynthesis Osteogenesis / drug effects* Osteoporosis / drug therapy* Rats Transforming Growth Factor beta / pharmacology
IF 2.985
引用数 14
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126)