| Summary: | 碩士 === 東吳大學 === 微生物學系 === 97 === Postmenopausal women have risks of getting osteoporosis because of estrogen efficiency. Hormone replacement therapy (HRT) can reduce bone loss efficiently, but long-term use of estrogen could have elevated risk of breast and endometrial cancer. Isoflavone is the major component in soybean and has similar structure with estrogen. Daily diet with abundant soybean can reduce age-related bone loss for postmenopausal women. In the present study, the gene expression effect of genistein and estrogen on mouse osteoblast cell line MC3T3-E1 were investigated. Suppression subtraction hybridization and gene array were used to analyze gene differential expression. Both genistein(10-8M) and estrogen10-9M) can stimulate cell proliferation. The genistein and estrogen induce different gene expression. From suppression subtraction hybridization, genistein was found to up-regulate growth factor GRN and LTBP2. In addition, genistein increased osteoblast marker COL1A2 expression. Estrogen can up-regulate EEF1A1 expression related to osteopontin (OPN) secretion. From gene array expression, it was found that genistein had different effects from estrogen expression on mRNA and protein level of ERβ/ ERα in ER-independent mechanism.Besides, the array data showed that estrogen can induce estrogen related receptorβ (ERRβ) expression. It thus suggested that estrogen might be through ERRβto regulate downstream gene expression. In ER-independent mechanism, genistein and estrogen could stimulate ERK/MEK signal pathway related genes expression. Estrogen could make ERK phorsphorylation level higher than genistein. Estrogen up-regulated PI3K mRNA expression related to AKT signal pathway and stimulated AKT phorsphorylation. In conclusion, the results showed that genistein and estrogen stimulated different gene expression level in MC3T3-E1 leaded to cell proliferation. This result may help to understand the benefit of genistein to treat osteoprosis compared with general estrogen replacement therapy.
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