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Genistein activates BMP‐Smad signaling pathway in MC3T3‐E1 cells
Author(s) -
Katsuyama Hironobu,
Fushimi Shigeko,
Yamane Kunikazu,
Hinenoya Hajime,
Akiyama Yuji,
Tomita Masafumi,
Okuyama Toshiko,
Watanabe Yoko,
Katsuyama Midori,
Saijoh Kiyofumi
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1053.3
Subject(s) - genistein , smad , noggin , chemistry , osteoprotegerin , signal transduction , phosphorylation , bone morphogenetic protein , bone morphogenetic protein 2 , medicine , endocrinology , microbiology and biotechnology , receptor , biology , biochemistry , in vitro , activator (genetics) , gene
Many epidemiological studies show that genistein intake is effective to maintain bone mineral density (BMD), so that the mechanisms underlying the effects of genistein on osteoblastic MC3T3‐E1 cells were investigated. Increase of osteoblastic MC3T3‐E1 cells were observed after administration of genistein. However, this increase was inhibited by ICI 182,780, inhibitor of estrogen. MC3T3‐E1 cells showed high alkaline phosphatase (ALP) activity after administration of genistein, indicating that genistein promoted estrogenic differentiation of MC3T3‐E1 cells. Production of osteoprotegerin (OPG), which is expressed by MC3T3‐E1 cells, was higher than control after administration of genistein by ELISA. Since OPG production was inhibited by noggin, inhibitor of BMP‐4, we investigated the BMP‐Smad signaling pathway. Genistein induced gene expression of BMP‐4. Moreover, immunofluorescence staining showed that genistein induced phosphorylation of Smad 1/5, a downstream molecule of BMP‐4, and noggin inhibited the phosphorylation of Smad 1/5. These results indicated that genistein might regulate osteoblastic function through BMP‐Smad signaling pathway as well as estrogen receptor pathway. This study was supported in part by a Research Project Grant (no. 21–204) from Kawasaki Medical School.