Genistein affects osteoblastic MC3T3-E1 cells both through estrogen receptor and BMP-Smad signaling pathways
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概要
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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.
- 2013-00-00
著者
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Katsuyama Hironobu
Department Of Public Health Kawasaki Medical College
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Nohno Tsutomu
Department Of Molecular Biology Kawasaki Medical School
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HINENOYA Hajime
Department of Public Health, Kawasaki Medical School
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Hinenoya Hajime
Department Of Anesthesiology And Intensive Care Medicine Kawasaki Medical School
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Nohno Tsutomu
Department of Molecular and Developmental Biology, Kawasaki Medical School
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