Regulation of Notch signaling genes during BMP2-induced differentiation of osteoblast precursor cells

被引:82
作者
de Jong, DS
Steegenga, WT
Hendriks, JMA
van Zoelen, EJJ [1 ]
Olijve, W
Dechering, KJ
机构
[1] Radboud Univ Nijmegen, Dept Cell Biol, Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Dept Appl Biol, Nijmegen, Netherlands
[3] NV Organon, Target Discovery Unit, Oss, Netherlands
关键词
osteoblast; BMP2; differentiation; notch; microarrays; transcription factors; signal transduction; TGF-beta;
D O I
10.1016/j.bbrc.2004.05.150
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The bone morphogenetic protein (BMP)-induced Smad signal transduction pathway is an important positive regulator of osteoblast differentiation. BMP and other members of the transforming growth factor-beta (TGF-beta) family have distinct effects on osteoblast differentiation, depending on cell type and cell differentiation status. In C2C12 mesenchymal cells, BMP-induced osteoblast differentiation can be blocked by TGF-beta. In a search for key regulators of osteoblast differentiation we have used microarray analysis to identify genes which are differentially regulated by BMP2 and TGF-beta. Within the first 24 h following the onset of differentiation, 61 BMP2-regulated genes were identified of which the BMP2 effect was counteracted by TGF-beta. The majority of these differentially expressed transcripts are related to signal transduction. Notably, our data show that three Notch signal transduction pathway genes, Lfng, Hey1, and Hes1, are differentially regulated by BMP2 and TGF-beta. This suggests that these genes might function as the focal point for interaction of Smad and Notch signaling during osteoblast differentiation. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:100 / 107
页数:8
相关论文
共 40 条
[1]   High bone mass in mice expressing a mutant LRP5 gene [J].
Babij, P ;
Zhao, WG ;
Small, C ;
Kharode, Y ;
Yaworsky, PJ ;
Bouxsein, ML ;
Reddy, PS ;
Bodine, PVN ;
Robinson, JA ;
Bhat, B ;
Marzolf, J ;
Moran, RA ;
Bex, F .
JOURNAL OF BONE AND MINERAL RESEARCH, 2003, 18 (06) :960-974
[2]   Activated β-catenin induces osteoblast differentiation of C3H10T1/2 cells and participates in BMP2 mediated signal transduction [J].
Bain, G ;
Müller, T ;
Wang, X ;
Papkoff, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 301 (01) :84-91
[3]   TGF-BETA ALTERS GROWTH AND DIFFERENTIATION-RELATED GENE-EXPRESSION IN PROLIFERATING OSTEOBLASTS IN-VITRO, PREVENTING DEVELOPMENT OF THE MATURE BONE PHENOTYPE [J].
BREEN, EC ;
IGNOTZ, RA ;
MCCABE, L ;
STEIN, JL ;
STEIN, GS ;
LIAN, JB .
JOURNAL OF CELLULAR PHYSIOLOGY, 1994, 160 (02) :323-335
[4]   Glycosyltransferase activity of fringe modulates notch-delta interactions [J].
Brückner, K ;
Perez, L ;
Clausen, H ;
Cohen, S .
NATURE, 2000, 406 (6794) :411-415
[5]   Microarray analysis of bone morphogenetic protein, transforming growth factor β, and activin early response genes during osteoblastic cell differentiation [J].
De Jong, DS ;
Van Zoelen, EJJ ;
Bauerschmidt, S ;
Olijve, W ;
Steegenga, WT .
JOURNAL OF BONE AND MINERAL RESEARCH, 2002, 17 (12) :2119-2129
[6]   Identification of novel regulators associated with early-phase osteoblast differentiation [J].
de Jong, DS ;
Vaes, BLT ;
Dechering, KJ ;
Feijen, A ;
Hendriks, JMA ;
Wehrens, R ;
Mummery, CL ;
van Zoelen, EJJ ;
Olijve, W ;
Steegenga, WT .
JOURNAL OF BONE AND MINERAL RESEARCH, 2004, 19 (06) :947-958
[7]   lunatic fringe is an essential mediator of somite segmentation and patterning [J].
Evrard, YA ;
Lun, Y ;
Aulehla, A ;
Gan, L ;
Johnson, RL .
NATURE, 1998, 394 (6691) :377-381
[8]   Roles of bone morphogenetic protein type I receptors and smad proteins in osteoblast and chondroblast differentiation [J].
Fujii, M ;
Takeda, K ;
Imamura, T ;
Aoki, H ;
Sampath, TK ;
Enomoto, S ;
Kawabata, M ;
Kato, M ;
Ichijo, H ;
Miyazono, K .
MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (11) :3801-3813
[9]   Local effects of transforming growth factor-β1 on rat calvaria:: Changes depending on the dose and the injection site [J].
Fujimoto, R ;
Tanizawa, T ;
Nishida, S ;
Yamamoto, N ;
Soshi, S ;
Endo, N ;
Takahashi, HE .
JOURNAL OF BONE AND MINERAL METABOLISM, 1999, 17 (01) :11-17
[10]   Activation of mitogen-activated protein kinase cascades is involved in regulation of bone morphogenetic protein-2-induced osteoblast differentiation in pluripotent C2Cl2 cells [J].
Gallea, S ;
Lallemand, F ;
Atfi, A ;
Rawadi, G ;
Ramez, V ;
Spinella-Jaegle, S ;
Kawai, S ;
Faucheu, C ;
Huet, L ;
Baron, R ;
Roman-Roman, S .
BONE, 2001, 28 (05) :491-498