Journal
JOURNAL OF BIOMOLECULAR SCREENING
Volume 14, Issue 10, Pages 1251-1256Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1087057109346446
Keywords
BMP2; upregulator; high-throughput screening; antiosteoporosis; phytoestrogen
Funding
- China Ministry of Science and Technology [2007DFA31370]
- National Commonwealth Research Institute Foundation
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Bone morphogenetic protein II (BMP2), a member of the transforming growth factor-beta (TGF-beta) superfamily, is highly expressed in osteoblasts and is a crucial regulator of osteogenic differentiation. Many observations clearly indicate the high potency of BMP2 as an inducer of osteogenesis, and it may be a novel therapeutic target for diseases associated with bone loss, especially in menopausal and postmenopausal women. to discover new agents that enhance the expression of the mouse BMP2, the authors developed a high-throughput assay to screen a synthetic and natural compound library. the cell-based high-throughput screen was conducted in 96-well plates using the clonal murine calvarial MC3T3-E1 cells. these cells were stably transfected with mouse BMP2 promoter-luciferase and calibrated with the known antiosteoporosis compound genistein. among 3192 compounds screened, 3 agents (daidzein, formononetin, and 2-Acetyldibenzothiophene) were picked up by the high-throughput screening assay, and those compounds were identified as upregulators of BMP2 expression by real-time quantitative reverse transcription-polymerase chain reaction and flow cytometry. thus, it is demonstrated that this screening model is useful for identifying lead compounds to treat osteoporosis and maintain bone metabolism balance. (Journal of Biomolecular Screening 2009:1251-1256)
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