Runx2 is a common target of transforming growth factor β1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12

被引:760
作者
Lee, KS
Kim, HJ
Li, QL
Chi, XZ
Ueta, C
Komori, T
Wozney, JM
Kim, EG
Choi, JY
Ryoo, HM
Bae, SC [1 ]
机构
[1] Chungbuk Natl Univ, Sch Med, Dept Biochem, Cheongju 361763, South Korea
[2] Chungbuk Natl Univ, Med Res Inst, Cheongju 361763, South Korea
[3] Kyungpook Natl Univ, Sch Dent, Dept Biochem, Taegu 702701, South Korea
[4] Kyungpook Natl Univ, Inst Med Res, Taegu 702701, South Korea
[5] Osaka Univ, Sch Med, Dept Med 3, Suita, Osaka 565, Japan
[6] Genet Inst Inc, Cambridge, MA USA
关键词
D O I
10.1128/MCB.20.23.8783-8792.2000
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
When C2C12 pluripotent mesenchymal precursor cells are treated with transforming growth factor beta2 (TGF-beta1), terminal differentiation into myotubes is blocked. Treatment with bone morphogenetic protein 2 (BMP-2) not only blocks myogenic differentiation of C2C12 cells but also induces osteoblast differentiation. The molecular mechanisms governing the ability of TGF-beta1 and BMP-2 to both induce ligand-specific responses and inhibit myogenic differentiation are not known. We identified Runx2/PEBP2 alphaA/Cbfa1, a global regulator of osteogenesis, as a major TGF-beta1-responsive element binding protein induced by TGF-beta1 and BMP-2 in C2C12 cells. Consistent with the observation that Runx2 can be induced by either TGF-beta1 or BMP-2, the exogenous expression of Runx2 mediated some of the effects of TGF-beta1 and BMP-2 but not osteoblast-specific gene expression, Runx2 mimicked common effects of TGF-beta1 and BMP-2 by inducing expression of matrix gene products (for example, collagen and fibronectin), suppressing MyoD expression, and inhibiting myotube formation of C2C12 cells. For osteoblast differentiation, an additional effector, BMP-specific Smad protein, was required. Our results indicate that Runx2 is a major target gene shared by TGF-beta and BMP signaling pathways and that the coordinated action of Runx2 and BMP-activated Smads leads to the induction of osteoblast-specific gene expression in C2C12 cells.
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页码:8783 / 8792
页数:10
相关论文
共 60 条
[21]   Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts [J].
Komori, T ;
Yagi, H ;
Nomura, S ;
Yamaguchi, A ;
Sasaki, K ;
Deguchi, K ;
Shimizu, Y ;
Bronson, RT ;
Gao, YH ;
Inada, M ;
Sato, M ;
Okamoto, R ;
Kitamura, Y ;
Yoshiki, S ;
Kishimoto, T .
CELL, 1997, 89 (05) :755-764
[22]   The fibronectin gene as a model for splicing and transcription studies [J].
Kornblihtt, AR ;
Pesce, CG ;
Alonso, CR ;
Cramer, P ;
Srebrow, A ;
Werbajh, S ;
Muro, AF .
FASEB JOURNAL, 1996, 10 (02) :248-257
[23]  
Lecka-Czernik B, 1999, J CELL BIOCHEM, V74, P357, DOI 10.1002/(SICI)1097-4644(19990901)74:3<357::AID-JCB5>3.0.CO
[24]  
2-7
[25]   Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia [J].
Lee, B ;
Thirunavukkarasu, K ;
Zhou, L ;
Pastore, L ;
Baldini, A ;
Hecht, J ;
Geoffroy, V ;
Ducy, P ;
Karsenty, G .
NATURE GENETICS, 1997, 16 (03) :307-310
[26]  
Lee MH, 1999, J CELL BIOCHEM, V73, P114, DOI 10.1002/(SICI)1097-4644(19990401)73:1<114::AID-JCB13>3.3.CO
[27]  
2-D
[28]   Smad2 overexpression enhances Smad4 gene expression and suppresses CBFA1 gene expression in osteoblastic osteosarcoma ROS17/2.8 cells and primary rat calvaria cells [J].
Li, J ;
Tsuji, K ;
Komori, T ;
Miyazono, K ;
Wrana, JL ;
Ito, Y ;
Nifuji, A ;
Noda, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (47) :31009-31015
[29]   STRUCTURE OF THE RAT OSTEOCALCIN GENE AND REGULATION OF VITAMIN-D-DEPENDENT EXPRESSION [J].
LIAN, J ;
STEWART, C ;
PUCHACZ, E ;
MACKOWIAK, S ;
SHALHOUB, V ;
COLLART, D ;
ZAMBETTI, G ;
STEIN, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (04) :1143-1147
[30]  
Lian JB, 1998, J CELL BIOCHEM, P62, DOI 10.1002/(SICI)1097-4644(1998)72:30/31+<62::AID-JCB10>3.0.CO