カツヤマ ヒロノブ
Hironobu Katsuyama
勝山 博信 所属 川崎医科大学 医学部 臨床医学 公衆衛生学 職種 教授 |
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論文種別 | 原著 |
言語種別 | |
査読の有無 | 査読あり |
表題 | Genistein affects osteoblastic MC3T3-E1 cells through estrogen receptor and BMP-Smad signaling pathways |
掲載誌名 | 正式名:Kawasaki Medical Journal ISSNコード:03850234 |
巻・号・頁 | 39(1),21-31頁 |
著者・共著者 | Hinenoya Hajime, Katsuyama Hironobu, Nohno Tsutomu |
担当区分 | 2nd著者,責任著者 |
発行年月 | 2013/03 |
概要 | ABSTRACT Many epidemiological studies show that genistein intake is effective for maintaining bone mineral density (BMD). Because the reason for the efficacy of genistein as a bone protective agent in vivo remains unclear, we investigated the mechanisms underlying the effects of genistein on BMD in relation to BMP-Smad signaling systems. When osteoblastic MC3T3-E1 cells were exposed to 1 μM genistein, they increased in number. Combined administrations of 1 μM genistein and 1 μM of ICI 182,780 inhibited the increase in cell numbers. Alkaline phosphatase (ALP) and Alizarin red staining showed high activities, indicating that genistein might promote estrogenic differentiation of MC3T3-E1 cells. Moreover, ELISA determined that production of osteoprotegerin (OPG), which is expressed by osteoblasts, was higher when 1 μM genistein was added to the medium than in controls. In contrast, when 10 ng/mL of noggin was administered in the medium, OPG production was inhibited. In order to clarify the underlying mechanism, we investigated the BMP-Smad signaling pathway. When genistein was added to the medium, it induced gene expression of BMP-4. Immunofluorescence staining showed that genistein induced phosphorylation of Smad 1/5, a downstream molecule of BMP. When noggin, which binds to BMP and blocks BMP signaling, was added to the medium, phosphorylation of Smad 1/5 was reduced. These results indicate that genistein may regulate bone metabolism through the BMP-Smad signaling pathway as well as through the estrogen receptor pathway. |