Transactivation of Core Binding Factor α1 as a Basic Mechanism to Trigger Parathyroid Hormone-Induced Osteogenesis
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概要
- 論文の詳細を見る
During 28-day culture of bone marrow- and calvaria-derived osteoblasts, the constant presence of parathyroid hormone (PTH)(1 - 34) retarded differentiation and nodule formation (NF) in a dose-dependent fashion (C-phase). In contrast, addition of PTH(1 - 34) in late stage cultures (from day 10 to 21) accelerated NF (A-phase). The stable production of such an A-phase allowed us to study the mechanism of bone anabolic action of PTH(1 - 34). Subcellular localization studies of core binding factor α1 (Cbfa1) and reporter assays provided the results indicating that in the A-phase, PTH(1 - 34) triggers its bone anabolic action via enhancement of Cbfa1 transactivation. RT-PCR and Northern blot analyses revealed that alkaline phosphatase, osteocalcin and bone sialoprotein expression decreased in the C-phase and increased in the A-phase; however, expression of other bone proteins (Cbfa1, PTH/PTH-related peptide-receptor, osteopontin, collagen I α1, collagen I α2, vitamin K-dependent γ-glutamyl carboxylase) did not change in a phase transition-related manner. Ovariectomized osteopenic mice, treated with PTH(1 - 34) (4 and 40 μg/kg, s.c., every other day, 4 or 6 weeks), recovered lost bone, displayed elevated nuclear localization of Cbfa1 in tibiae without alteration of its cytosolic level and exhibited upregulation of expressions of the same set of proteins (alkaline phosphatase, osteocalcin and bone sialoprotein) in femora. These results obtained by a concerted study in vitro and in vivo suggest that PTH triggers its osteogenic action via promotion of the transactivation of Cbfa1.
- 社団法人 日本薬理学会の論文
- 2001-08-01
著者
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Fujita Takashi
Department Of Cardiology Kanazawa University
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NAKAMUTA HIROMICHI
Department of Parmacology, Setsunan University
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KOIDA MASAO
Department of Parmacology, Setsunan University
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Fujita T
Division Of Oral Cytology And Cell Biology Department Of Developmental And Reconstructive Medicine N
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FUJITA Takuya
Ritsumeikan University College of Information Science and Engeneering
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FUKUYAMA Ryo
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
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IZUMO Nobuo
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
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HIRAI Takao
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
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MEGURO Toru
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University
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Fujita T
Ritsumeikan University College Of Information Science And Engeneering
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Izumo Nobuo
Department Of Pharmacology Daiichi College Of Pharmaceutical Sciences
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Meguro Toru
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Setsunan University
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Meguro Toru
Department Of Pathology Yamagata University School Of Medicine
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Koida M
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Setsunan University
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Koida Masao
Department Of Parmacology Setsunan University
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Hirai Takao
Department Of Molecular Pharmacology Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama Univer
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Hirai Takao
Department Of Otorhinolaryngology Hiroshima University School Of Medicine
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Fukuyama Tohru
Department Of Pharmacology Hiroshima International University
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Fukushima Tohru
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Setsunan University
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Nakamuta H
Department Of Pharmacology Hiroshima International University
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Nakamuta Hiromichi
Department Of Parmacology Setsunan University
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Fujita Takashi
Department Of Breast Oncology Aichi Cancer Center Hospital
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Fujita Takashi
Department Of Biological Sciences Graduate School Of Science The University Of Tokyo
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Fujita Takashi
Department Of Biochemistry The University Of Sydney
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Fujita Takashi
Department Of Anesthesiology Suwa Red Cross Hospital
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