| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 280, Issue 39, 33132-33140, September 30, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1
From the
Department of Cell Biology and the Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0106 and the Women's Health Research Institute, Wyeth Research, Collegeville, Pennsylvania 19426
Both activating and null mutations of proteins required for canonical WNT signaling have revealed the importance of this pathway for normal skeletal development. However, tissue-specific transcriptional mechanisms through which WNT signaling promotes the differentiation of bone-forming cells have yet to be identified. Here, we address the hypothesis that canonical WNT signaling and the bone-related transcription factor RUNX2/CBFA1/AML3 are functionally linked components of a pathway required for the onset of osteoblast differentiation. Our findings show that, in bone of the SFRP1 (secreted frizzled-related protein-1)-null mouse, which exhibits activated WNT signaling and a high bone mass phenotype, there is a significant increase in expression of T-cell factor (TCF)-1, Runx2, and the RUNX2 target gene osteocalcin. We demonstrate by mutational analysis that a functional TCF regulatory element responsive to canonical WNT signaling resides in the promoter of the Runx2 gene (–97 to –93). By chromatin immunoprecipitation, recruitment of 
-catenin and TCF1 to the endogenous Runx2 gene is shown. Coexpression of TCF1 with canonical WNT proteins resulted in a 2–5-fold activation of Runx2 promoter activity and a 7–8-fold induction of endogenous mRNA in mouse pluripotent mesenchymal and osteoprogenitor cells. This enhancement was abrogated by SFRP1. Taken together, our results provide evidence for direct regulation of Runx2 by canonical WNT signaling and suggest that Runx2 is a target of -catenin/TCF1 for the stimulation of bone formation. We propose that WNT/TCF1 signaling, like bone morphogenetic protein/transforming growth factor- signaling, activates Runx2 gene expression in mesenchymal cells for the control of osteoblast differentiation and skeletal development.
Received for publication, January 18, 2005 , and in revised form, June 3, 2005.
* This work was supported by National Institutes of Health Grants AR39588, P01 AR48818, and P30 DK32520. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed: Dept. of Cell Biology and the Cancer Center, University of Massachusetts Medical School, 55 Lake Ave. North, Worcester, MA 01655-0106. Tel.: 508-856-5625; Fax: 508-856-6800; E-mail: jane.lian{at}umassmed.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. Li, M. Q. Hassan, S. Volinia, A. J. van Wijnen, J. L. Stein, C. M. Croce, J. B. Lian, and G. S. Stein A microRNA signature for a BMP2-induced osteoblast lineage commitment program PNAS, September 16, 2008; 105(37): 13906 - 13911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ambrosetti, G. Holmes, A. Mansukhani, and C. Basilico Fibroblast Growth Factor Signaling Uses Multiple Mechanisms To Inhibit Wnt-Induced Transcription in Osteoblasts Mol. Cell. Biol., August 1, 2008; 28(15): 4759 - 4771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-L. Cheng, J.-S. Shao, J. Cai, O. L. Sierra, and D. A. Towler Msx2 Exerts Bone Anabolism via Canonical Wnt Signaling J. Biol. Chem., July 18, 2008; 283(29): 20505 - 20522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.L. Scheller, J. Chang, and C.Y. Wang Wnt/{beta}-catenin Inhibits Dental Pulp Stem Cell Differentiation J. Dent. Res., February 1, 2008; 87(2): 126 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhou, W. Mak, Y. Zheng, C. R. Dunstan, and M. J. Seibel Osteoblasts Directly Control Lineage Commitment of Mesenchymal Progenitor Cells through Wnt Signaling J. Biol. Chem., January 25, 2008; 283(4): 1936 - 1945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. H. Nissen-Meyer, R. Jemtland, V. T. Gautvik, M. E. Pedersen, R. Paro, D. Fortunati, D. D. Pierroz, V. A. Stadelmann, S. Reppe, F. P. Reinholt, et al. Osteopenia, decreased bone formation and impaired osteoblast development in Sox4 heterozygous mice J. Cell Sci., August 15, 2007; 120(16): 2785 - 2795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-H. Liu, A. Kirschenbaum, S. Yao, G. Liu, S. A. Aaronson, and A. C. Levine Androgen-Induced Wnt Signaling in Preosteoblasts Promotes the Growth of MDA-PCa-2b Human Prostate Cancer Cells Cancer Res., June 15, 2007; 67(12): 5747 - 5753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Glass II and G. Karsenty In Vivo Analysis of Wnt Signaling in Bone Endocrinology, June 1, 2007; 148(6): 2630 - 2634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Q. Hassan, R. Tare, S. H. Lee, M. Mandeville, B. Weiner, M. Montecino, A. J. van Wijnen, J. L. Stein, G. S. Stein, and J. B. Lian HOXA10 Controls Osteoblastogenesis by Directly Activating Bone Regulatory and Phenotypic Genes Mol. Cell. Biol., May 1, 2007; 27(9): 3337 - 3352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. V. Bodine Wnt Signaling in Bone IBMS BoneKEy, March 1, 2007; 4(3): 108 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Reinhold and M. C. Naski Direct Interactions of Runx2 and Canonical Wnt Signaling Induce FGF18 J. Biol. Chem., February 9, 2007; 282(6): 3653 - 3663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Q. Hassan, R. S. Tare, S. H. Lee, M. Mandeville, M. I. Morasso, A. Javed, A. J. van Wijnen, J. L. Stein, G. S. Stein, and J. B. Lian BMP2 Commitment to the Osteogenic Lineage Involves Activation of Runx2 by DLX3 and a Homeodomain Transcriptional Network J. Biol. Chem., December 29, 2006; 281(52): 40515 - 40526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Giuliani, V. Rizzoli, and G. D. Roodman Multiple myeloma bone disease: pathophysiology of osteoblast inhibition Blood, December 15, 2006; 108(13): 3992 - 3996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Plaisance, A. Abderrahmani, V. Perret-Menoud, P. Jacquemin, F. Lemaigre, and R. Regazzi MicroRNA-9 Controls the Expression of Granuphilin/Slp4 and the Secretory Response of Insulin-producing Cells J. Biol. Chem., September 15, 2006; 281(37): 26932 - 26942. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Rodda and A. P. McMahon Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors Development, August 15, 2006; 133(16): 3231 - 3244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Spater, T. P. Hill, R. J. O'Sullivan, M. Gruber, D. A. Conner, and C. Hartmann Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis Development, August 1, 2006; 133(15): 3039 - 3049. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Hernandez-Gonzalez, I. Gonzalez-Robayna, M. Shimada, C. M. Wayne, S. A. Ochsner, L. White, and J. S. Richards Gene Expression Profiles of Cumulus Cell Oocyte Complexes during Ovulation Reveal Cumulus Cells Express Neuronal and Immune-Related Genes: Does this Expand Their Role in the Ovulation Process? Mol. Endocrinol., June 1, 2006; 20(6): 1300 - 1321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Demer and Y. Tintut Pitting Phosphate Transport Inhibitors Against Vascular Calcification Circ. Res., April 14, 2006; 98(7): 857 - 859. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
