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Development ePress online publication date 2 Dec 2004
doi: 10.1242/dev.01564
Research article
Sequential roles of Hedgehog and Wnt signaling in osteoblast development
Hongliang Hu,
Matthew J. Hilton,
Xiaolin Tu,
Kai Yu,
David M. Ornitz,
and
Fanxin Long*
* Author for correspondence (e-mail: flong{at}wustl.edu)
Signals that govern development of the osteoblast lineage are not well understood. Indian hedgehog (Ihh), a member of the hedgehog (Hh) family of proteins, is essential for osteogenesis in the endochondral skeleton during embryogenesis. The canonical pathway of Wnt signaling has been implicated by studies of Lrp5, a co-receptor for Wnt proteins, in postnatal bone mass homeostasis. In the present study we demonstrate that
-catenin, a central player in the canonical Wnt pathway, is indispensable for osteoblast differentiation in the mouse embryo. Moreover, we present evidence that Wnt signaling functions downstream of Ihh in development of the osteoblast lineage. Finally Wnt7b is identified as a potential endogenous ligand regulating osteogenesis. These data support a model that integrates Hh and Wnt signaling in the regulation of osteoblast development.

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 |
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|
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 |
|

|
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|
 |
|

|
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|
 |
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|
 |

|
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|
 |
|

|
 |

|
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|
 |
|

|
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|
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|
 |
|

|
 |

|
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|
 |
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
 |
|

|
 |

|
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134(18):
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|
 |
|

|
 |

|
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J. Biol. Chem.,
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282(37):
27298 - 27305.
[Abstract]
[Full Text]
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|
 |
|

|
 |

|
 |
 
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101(6):
581 - 589.
[Abstract]
[Full Text]
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|
 |
|

|
 |

|
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D. A. Glass II and G. Karsenty
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148(6):
2630 - 2634.
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[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Kang, C. N. Bennett, I. Gerin, L. A. Rapp, K. D. Hankenson, and O. A. MacDougald
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J. Biol. Chem.,
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282(19):
14515 - 14524.
[Abstract]
[Full Text]
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|
 |
|

|
 |

|
 |
 
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8959 - 8968.
[Abstract]
[Full Text]
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|
 |
|

|
 |

|
 |
 
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J. Biol. Chem.,
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3653 - 3663.
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[Full Text]
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|
 |
|

|
 |

|
 |
 
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Dickkopf Homolog 1 Mediates Endothelin-1-Stimulated New Bone Formation
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21(2):
486 - 498.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Intraflagellar transport is essential for endochondral bone formation
Development,
January 15, 2007;
134(2):
307 - 316.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. N. Pearse
Wnt antagonism in multiple myeloma: a potential cause of uncoupled bone remodeling.
Clin. Cancer Res.,
October 15, 2006;
12(20):
6274s - 6278s.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. K. Mak, M.-H. Chen, T. F. Day, P.-T. Chuang, and Y. Yang
Wnt/{beta}-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation
Development,
September 15, 2006;
133(18):
3695 - 3707.
[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]
|
 |
|

|
 |

|
 |
 
J.-S. Shao, J. Cai, and D. A. Towler
Molecular Mechanisms of Vascular Calcification: Lessons Learned From The Aorta
Arterioscler Thromb Vasc Biol,
July 1, 2006;
26(7):
1423 - 1430.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. I. Reinhold, R. M. Kapadia, Z. Liao, and M. C. Naski
The Wnt-inducible Transcription Factor Twist1 Inhibits Chondrogenesis
J. Biol. Chem.,
January 20, 2006;
281(3):
1381 - 1388.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Schipani, A. Zallone, G. J. Strewler, J. W. Pike, S. Ferrari, Y. Jiang, and E. Seeman
Meeting Report from the 27th Annual Meeting of the American Society for Bone and Mineral Research: September 23-27, 2005 in Nashville, Tennessee, USA
IBMS BoneKEy,
January 1, 2006;
3(1):
29 - 62.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Hilton, X. Tu, J. Cook, H. Hu, and F. Long
Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development
Development,
October 1, 2005;
132(19):
4339 - 4351.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Gaur, C. J. Lengner, H. Hovhannisyan, R. A. Bhat, P. V. N. Bodine, B. S. Komm, A. Javed, A. J. van Wijnen, J. L. Stein, G. S. Stein, et al.
Canonical WNT Signaling Promotes Osteogenesis by Directly Stimulating Runx2 Gene Expression
J. Biol. Chem.,
September 30, 2005;
280(39):
33132 - 33140.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Ai, S. L. Holmen, W. Van Hul, B. O. Williams, and M. L. Warman
Reduced Affinity to and Inhibition by DKK1 Form a Common Mechanism by Which High Bone Mass-Associated Missense Mutations in LRP5 Affect Canonical Wnt Signaling
Mol. Cell. Biol.,
June 15, 2005;
25(12):
4946 - 4955.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Kobayashi and H. Kronenberg
Minireview: Transcriptional Regulation in Development of Bone
Endocrinology,
March 1, 2005;
146(3):
1012 - 1017.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Seeman and G. J. Strewler
Clinical and Basic Research Papers - December 2004 Selections
IBMS BoneKEy,
January 1, 2005;
2(1):
1 - 5.
[Full Text]
[PDF]
|
 |
|
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