JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on June 20, 2003 Originally published In Press as doi:10.1074/jbc.M211610200 on April 18, 2003
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
278/26/23270    most recent
M211610200v2
M211610200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jeon, M. J.
Right arrow Articles by Shin, C. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jeon, M. J.
Right arrow Articles by Shin, C. S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Papers In Press, published online ahead of print April 21, 2003
J. Biol. Chem, 10.1074/jbc.M211610200
Submitted on November 14, 2002
Revised on April 15, 2003
Accepted on April 21, 2003

Activation of peroxisome proliferator-activated receptor-gamma inhibits the Runx2-mediated transcription of osteocalcin in osteoblasts

Min Jae Jeon, Jeong Ah Kim, Sung Hee Kwon, Sang Wan Kim, Kyong Soo Park, Sung-Woo Park, Seong Yeon Kim, and Chan Soo Shin

Internal Medicine, Seoul National University College of Medicine, Seoul 110-744

Corresponding Author: csshin{at}plaza.snu.ac.kr

Mesenchymal cells are able to differentiate into several distinct cell types, including osteoblasts and adipocytes. The commitment to a particular lineage may be regulated by specific transcription factors. Peroxisome proliferator activated receptor ã (PPARã) acting in conjunction with C/EBPá has been suggested as a key regulator of adipogenic differentiation. Previous studies have shown that the activation of PPARã in osteoblasts suppresses osteoblast differentiation and the expression of osteocalcin, one of the osteoblast-specific proteins. However, the mechanism of this inhibition remains unclear. We investigated the effect of PPARã activation on the expression of osteocalcin and analyzed the underlying molecular mechanism. Mouse osteoblastic cell line MC3T3-E1 cells express PPARã, which is transcriptionally active, whereas rat osteosarcoma cell line, ROS 17/2.8 does not. Treatment of MC3T3-E1 osteoblasts and ROS 17/2.8 cells stably transfected with PPARã2 with the PPARã activator, 15-deoxy-Ä12,14 prostaglandin J2 (15d-PGJ2), inhibited the mRNA expression of osteocalcin and Runx2, the latter of which is a key transcription factor in the osteoblastic differentiation. These decreased expressions of osteocalcin and Runx2 were partly explained by the decreased abundance of Runx2 resulting from the suppressed transcription from Runx2 promoter. However, in addition to this indirect effect, the activation of PPARã by 15d-PGJ2 directly suppressed the Runx2-mediated induction of osteocalcin promoter activity and of the activity of the artificial promoter p6OSE2, which contained six tandem copies of the OSE2 element, the Runx2-binding promoter sequence. This inhibition was found to be mediated by a physical interaction between PPARã and Runx2 and the subsequent repression of the transcriptional activity of the OSE2 sequence. Thus, this study demonstrates that the activation of PPARã inhibits osteocalcin expression both by suppressing the expression of Runx2 and by interfering with the transactivation ability of Runx2.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 JCBHome page
X. Li, M. Huang, H. Zheng, Y. Wang, F. Ren, Y. Shang, Y. Zhai, D. M. Irwin, Y. Shi, D. Chen, et al.
CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation
J. Cell Biol., October 21, 2008; 181(6): 959 - 972.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Kang, C. N. Bennett, I. Gerin, L. A. Rapp, K. D. Hankenson, and O. A. MacDougald
Wnt Signaling Stimulates Osteoblastogenesis of Mesenchymal Precursors by Suppressing CCAAT/Enhancer-binding Protein {alpha} and Peroxisome Proliferator-activated Receptor {gamma}
J. Biol. Chem., May 11, 2007; 282(19): 14515 - 14524.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
D. Kim, S. W. Cho, S. J. Her, J. Y. Yang, S. W. Kim, S. Y. Kim, and C. S. Shin
Retrovirus-Mediated Gene Transfer of Receptor Activator of Nuclear Factor-{kappa}B-Fc Prevents Bone Loss in Ovariectomized Mice
Stem Cells, July 1, 2006; 24(7): 1798 - 1805.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
C. S. Shin, M. J. Jeon, J.-Y. Yang, S.-J. Her, D. Kim, S. W. Kim, and S. Y. Kim
CCAAT/enhancer-binding protein {delta} activates the Runx2-mediated transcription of mouse osteocalcin II promoter.
J. Mol. Endocrinol., June 1, 2006; 36(3): 531 - 546.
[Abstract] [Full Text] [PDF]

Home page
 IBMS BoneKEyHome page
G. A. Rodan and A. R. Rodan
The Family of Osteoblast Transcription Factors is Growing
IBMS BoneKEy, October 1, 2005; 2(10): 12 - 15.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. N. Bennett, K. A. Longo, W. S. Wright, L. J. Suva, T. F. Lane, K. D. Hankenson, and O. A. MacDougald
Regulation of osteoblastogenesis and bone mass by Wnt10b
PNAS, March 1, 2005; 102(9): 3324 - 3329.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z.-S. Xiao, A. B. Hjelmeland, and L. D. Quarles
Selective Deficiency of the "Bone-related" Runx2-II Unexpectedly Preserves Osteoblast-mediated Skeletogenesis
J. Biol. Chem., May 7, 2004; 279(19): 20307 - 20313.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.