caa a22 4500 605462917 CHVBK 20210128100250.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00774-014-0567-9 doi (NATIONALLICENCE)springer-10.1007/s00774-014-0567-9 Estrogen stimuli promote osteoblastic differentiation via the subtilisin-like proprotein convertase PACE4 in MC3T3-E1 cells [Elektronische Daten] [Hyejin Kim, Atsushi Tabata, Toshifumi Tomoyasu, Tomomi Ueno, Shigeto Uchiyama, Keizo Yuasa, Akihiko Tsuji, Hideaki Nagamune] Estrogenic compounds include endogenous estrogens such as estradiol as well as soybean isoflavones, such as daidzein and its metabolite equol, which are known phytoestrogens that prevent osteoporosis in postmenopausal women. Indeed, mineralization of MC3T3-E1 cells, a murine osteoblastic cell line, was significantly decreased in medium containing fetal bovine serum treated with charcoal-dextran to deplete endogenous estrogens, but estradiol and these soybean isoflavones dose-dependently restored the differentiation of MC3T3-E1 cells; equol was tenfold more effective than daidzein. These differentiation-promoting effects were inhibited by the addition of fulvestrant, which is a selective downregulator of estrogen receptors. Analysis of the expression pattern of bone-related genes by reverse transcription PCR (RT-PCR)/quantitative real-time PCR (qRT-PCR), which focused on responsiveness to the estrogen stimuli, revealed that the transcription of PACE4, a subtilisin-like proprotein convertase, was tightly linked with the differentiation of MC3T3-E1 cells induced by estrogen stimuli. Moreover, treatment with RNAi of PACE4 in MC3T3-E1 cells resulted in a drastic decrease of mineralization in the presence of estrogen stimuli. These results strongly suggest that PACE4 participates in bone formation at least in osteoblast differentiation, and estrogen receptor-mediated stimuli induce osteoblast differentiation through the upregulation of PACE4 expression. The Japanese Society for Bone and Mineral Research and Springer Japan, 2014 Osteoblast nationallicence PACE4 nationallicence Estrogen nationallicence Soybean isoflavone nationallicence Kim Hyejin Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut Tabata Atsushi Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut Tomoyasu Toshifumi Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut Ueno Tomomi Saga Nutraceuticals Research Institute, Otsuka Pharmaceutical Co., Ltd, Saga, Japan aut Uchiyama Shigeto Saga Nutraceuticals Research Institute, Otsuka Pharmaceutical Co., Ltd, Saga, Japan aut Yuasa Keizo Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut Tsuji Akihiko Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut Nagamune Hideaki Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut Journal of Bone and Mineral Metabolism Springer Japan 33/1(2015-01-01), 30-39 0914-8779 33:1<30 2015 33 774 https://doi.org/10.1007/s00774-014-0567-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00774-014-0567-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kim Hyejin Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut NATIONALLICENCE 700 1- Tabata Atsushi Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut NATIONALLICENCE 700 1- Tomoyasu Toshifumi Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut NATIONALLICENCE 700 1- Ueno Tomomi Saga Nutraceuticals Research Institute, Otsuka Pharmaceutical Co., Ltd, Saga, Japan aut NATIONALLICENCE 700 1- Uchiyama Shigeto Saga Nutraceuticals Research Institute, Otsuka Pharmaceutical Co., Ltd, Saga, Japan aut NATIONALLICENCE 700 1- Yuasa Keizo Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut NATIONALLICENCE 700 1- Tsuji Akihiko Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut NATIONALLICENCE 700 1- Nagamune Hideaki Department of Biological Science and Technology, Institute of Technology and Science, The University of Tokushima Graduate School, #2-1, Minami-josanjima, 770-8506, Tokushima, Japan aut NATIONALLICENCE 773 0- Journal of Bone and Mineral Metabolism Springer Japan 33/1(2015-01-01), 30-39 0914-8779 33:1<30 2015 33 774