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http://dx.doi.org/10.5483/BMBRep.2014.47.8.225

GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2  

Song, Insun (Department of Biochemistry, Ajou University School of Medicine, The Graduate School, Ajou University)
Kim, Kabsun (Department of Pharmacology, Chonnam National University Medical School)
Kim, Jung Ha (Department of Pharmacology, Chonnam National University Medical School)
Lee, Young-Kyoung (Department of Biochemistry, Ajou University School of Medicine, The Graduate School, Ajou University)
Jung, Hyun-Jung (Department of Biochemistry, Ajou University School of Medicine, The Graduate School, Ajou University)
Byun, Hae-Ok (Department of Biochemistry, Ajou University School of Medicine, The Graduate School, Ajou University)
Yoon, Gyesoon (Department of Biochemistry, Ajou University School of Medicine, The Graduate School, Ajou University)
Kim, Nacksung (Department of Pharmacology, Chonnam National University Medical School)
Publication Information
BMB Reports / v.47, no.8, 2014 , pp. 463-468 More about this Journal
Abstract
Osteoblasts are specialized mesenchymal cells that are responsible for bone formation. In this study, we examine the role of GATA4 in osteoblast differentiation. GATA4 was abundantly expressed in preosteoblast cells and gradually down-regulated during osteoblast differentiation. Overexpression of GATA4 in osteoblastic cells inhibited alkaline phosphatase activity and nodule formation in osteogenic conditioned cell culture system. In addition, overexpression of GATA4 attenuated expression of osteogenic marker genes, including Runx2, alkaline phosphatase, bone sialoprotein, and osteocalcin, all of which are important for osteoblast differentiation and function. Overexpression of GATA4 attenuated Runx2 promoter activity, whereas silencing of GATA4 increased Runx2 induction. We found that GATA4 interacted with Dlx5 and subsequently decreased Dlx5 binding activity to Runx2 promoter region. Our data suggest that GATA4 acts as a negative regulator in osteoblast differentiation by downregulation of Runx2.
Keywords
GATA4; Transcription factor; Runx2; Dlx5; Osteoblast differentiation;
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1 Molkentin, J. D., Lu, J. R., Antos, C. L., Markham, B., Richardson, J., Robbins, J., Grant, S. R. and Olson, E. N. (1998) A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 93, 215-228.   DOI   ScienceOn
2 Song, I., Kim, B. S., Kim, C. S. and Im, G. I. (2011) Effects of BMP-2 and vitamin D3 on the osteogenic differentiation of adipose stem cells. Biochem. Biophys. Res. Commun. 408, 126-131.   DOI   ScienceOn
3 Miranda-Carboni, G. A., Guemes, M., Bailey, S., Anaya, E., Corselli, M., Peault, B. and Krum, S. A. (2011) GATA4 regulates estrogen receptor-alpha-mediated osteoblast transcription. Mol. Endocrinol. 25, 1126-1136.   DOI   ScienceOn
4 Bisping, E., Ikeda, S., Kong, S. W., Tarnavski, O., Bodyak, N., McMullen, J. R., Rajagopal, S., Son, J. K., Ma, Q., Springer, Z., Kang, P. M., Izumo, S. and Pu, W. T. (2006) Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure. Proc. Natl. Acad. Sci. U. S. A. 103, 14471-14476.   DOI   ScienceOn
5 Katz, A. M. (1995) The cardiomyopathy of overload: an unnatural growth response. Eur. Heart J. 16(Suppl O), 110-114.
6 Tadic, T., Dodig, M., Erceg, I., Marijanovic, I., Mina, M., Kalajzic, Z., Velonis, D., Kronenberg, M. S., Kosher, R. A., Ferrari, D. and Lichtler, A. C. (2002) Overexpression of Dlx5 in chicken calvarial cells accelerates osteoblastic differentiation. J. Bone Miner. Res. 17, 1008-1014.   DOI   ScienceOn
7 Lee, M. H., Kim, Y. J., Yoon, W. J., Kim, J. I., Kim, B. G., Hwang, Y. S., Wozney, J. M., Chi, X. Z., Bae, S. C., Choi, K. Y., Cho, J. Y., Choi, J. Y. and Ryoo, H. M. (2005) Dlx5 specifically regulates Runx2 type II expression by binding to homeodomain-response elements in the Runx2 distal promoter. J. Biol. Chem. 280, 35579-35587.   DOI   ScienceOn
8 Lee, M. H., Kim, Y. J., Kim, H. J., Park, H. D., Kang, A. R., Kyung, H. M., Sung, J. H., Wozney, J. M., Kim, H. J. and Ryoo, H. M. (2003) BMP-2-induced Runx2 expression is mediated by Dlx5, and TGF-beta 1 opposes the BMP-2-induced osteoblast differentiation by suppression of Dlx5 expression. J. Biol. Chem. 278, 34387-34394.   DOI   ScienceOn
9 Molkentin, J. D. (2000) The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression. J. Biol. Chem. 275, 38949-38952.   DOI   ScienceOn
10 Viger, R. S., Guittot, S. M., Anttonen, M., Wilson, D. B. and Heikinheimo, M. (2008) Role of the GATA family of transcription factors in endocrine development, function, and disease. Mol. Endocrinol. 22, 781-798.   DOI   ScienceOn
11 Pikkarainen, S., Tokola, H., Kerkela, R. and Ruskoaho, H. (2004) GATA transcription factors in the developing and adult heart. Cardiovasc. Res. 63, 196-207.   DOI   ScienceOn
12 Zhou, G., Zheng, Q., Engin, F., Munivez, E., Chen, Y., Sebald, E., Krakow, D. and Lee, B. (2006) Dominance of SOX9 function over RUNX2 during skeletogenesis. Proc. Natl. Acad. Sci. U. S. A. 103, 19004-19009.   DOI   ScienceOn
13 Samee, N., de Vernejoul, M. C. and Levi, G. (2007) Role of DLX regulatory proteins in osteogenesis and chondrogenesis. Crit. Rev. Eukaryot. Gene Expr. 17, 173-186.   DOI
14 Otto, F., Thornell, A. P., Crompton, T., Denzel, A., Gilmour, K. C., Rosewell, I. R., Stamp, G. W., Beddington, R. S., Mundlos, S., Olsen, B. R., Selby, P. B. and Owen, M. J. (1997) Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89, 765-771.   DOI   ScienceOn
15 Lee, B., Thirunavukkarasu, K., Zhou, L., Pastore, L., Baldini, A., Hecht, J., Geoffroy, V., Ducy, P. and Karsenty, G. (1997) Missense mutations abolishing DNA binding of the osteoblast- specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia. Nat. Genet. 16, 307-310.   DOI   ScienceOn
16 Marie, P. J. (2008) Transcription factors controlling osteoblastogenesis. Arch. Biochem. Biophys. 473, 98-105.   DOI   ScienceOn
17 Zhao, G. Q., Zhao, S., Zhou, X., Eberspaecher, H., Solursh, M. and de Crombrugghe, B. (1994) rDlx, a novel distal- less-like homeoprotein is expressed in developing cartilages and discrete neuronal tissues. Dev. Biol. 164, 37-51.   DOI   ScienceOn
18 Holleville, N., Mateos, S., Bontoux, M., Bollerot, K. and Monsoro-Burq, A. H. (2007) Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture mesenchyme. Dev. Biol. 304, 860-874.   DOI   ScienceOn
19 Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., Shimizu, Y., Bronson, R. T., Gao, Y. H., Inada, M., Sato, M., Okamoto, R., Kitamura, Y., Yoshiki, S. and Kishimoto, T. (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89, 755-764.   DOI   ScienceOn
20 Miyama, K., Yamada, G., Yamamoto, T. S., Takagi, C., Miyado, K., Sakai, M., Ueno, N. and Shibuya, H. (1999) A BMP-inducible gene, dlx5, regulates osteoblast differentiation and mesoderm induction. Dev. Biol. 208, 123-133.   DOI   ScienceOn
21 Hong, J. H., Hwang, E. S., McManus, M. T., Amsterdam, A., Tian, Y., Kalmukova, R., Mueller, E., Benjamin, T., Spiegelman, B. M., Sharp, P. A., Hopkins, N. and Yaffe, M. B. (2005) TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 309, 1074-1078.   DOI   ScienceOn