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Roles of bone morphogenetic protein type I receptors and Smad proteins in osteoblast and chondroblast differentiation.

Authors :
M, Fujii
K, Takeda
T, Imamura
H, Aoki
K, Sampath T
S, Enomoto
M, Kawabata
M, Kato
H, Ichijo
K, Miyazono
Source :
Molecular Biology of the Cell; November 1999, Vol. 10 Issue: 11 p3801-13, 13p
Publication Year :
1999

Abstract

The biological effects of type I serine/threonine kinase receptors and Smad proteins were examined using an adenovirus-based vector system. Constitutively active forms of bone morphogenetic protein (BMP) type I receptors (BMPR-IA and BMPR-IB; BMPR-I group) and those of activin receptor-like kinase (ALK)-1 and ALK-2 (ALK-1 group) induced alkaline phosphatase activity in C2C12 cells. Receptor-regulated Smads (R-Smads) that act in the BMP pathways, such as Smad1 and Smad5, also induced the alkaline phosphatase activity in C2C12 cells. BMP-6 dramatically enhanced alkaline phosphatase activity induced by Smad1 or Smad5, probably because of the nuclear translocation of R-Smads triggered by the ligand. Inhibitory Smads, i.e., Smad6 and Smad7, repressed the alkaline phosphatase activity induced by BMP-6 or the type I receptors. Chondrogenic differentiation of ATDC5 cells was induced by the receptors of the BMPR-I group but not by those of the ALK-1 group. However, kinase-inactive forms of the receptors of the ALK-1 and BMPR-I groups blocked chondrogenic differentiation. Although R-Smads failed to induce cartilage nodule formation, inhibitory Smads blocked it. Osteoblast differentiation induced by BMPs is thus mediated mainly via the Smad-signaling pathway, whereas chondrogenic differentiation may be transmitted by Smad-dependent and independent pathways.

Details

Language :
English
ISSN :
10591524 and 19394586
Volume :
10
Issue :
11
Database :
Supplemental Index
Journal :
Molecular Biology of the Cell
Publication Type :
Periodical
Accession number :
ejs7033431