Transactivation of Core Binding Factor α1 as a Basic Mechanism to Trigger Parathyroid Hormone-Induced Osteogenesis

• Fujita Takashi

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University

• Fukuyama Ryo

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University

• Izumo Nobuo

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University

• Hirai Takao

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University

• Meguro Toru

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University

• Nakamuta Hiromichi

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University

• Koida Masao

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University

書誌事項

タイトル別名

• Transactivation of Core Binding Factor .ALPHA.1 as a Basic Mechanism to Trigger Parathyroid Hormone-Induced Osteogenesis.
• Transactivation of Core Binding Factor アルファ 1 as a Basic Mechanism to Trigger Parathyroid Hormone Induced Osteogenesis

抄録

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.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 86 (4), 405-416, 2001

  公益社団法人 日本薬理学会

キーワード

• Parathyroid hormone
• Osteogenesis
• Osteoblast
• Core binding factor α1
• Transactivation

詳細情報

• CRID: 1390001204287764224
• NII論文ID: 10007123240
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.86.405
• COI: 1:CAS:528:DC%2BD3MXmtlCgsrs%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL書誌ID: 5885847
• PubMed: 11569614
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I5885847
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819303269?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819303269?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2002079348
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可