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

The Japanese Journal of Pharmacology

Takao Hirai¹  Toru Meguro¹  Takashi Fujita¹  Hiromichi Nakamuta¹  Ryo Fukuyama¹  Masao Koida¹  Nobuo Izumo¹ 

[1] Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University

关键词: Parathyroid hormone;    Osteogenesis;    Osteoblast;    Core binding factor α1;    Transactivation;   

DOI  :  10.1254/jjp.86.405

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(38)Cited-By(11)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.

【 授权许可】

Unknown