|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online August 25, 2006
doi: 10.1242/10.1242/dev.02546
1 Genetic Disease Research Branch, National Human Genome Research Institute,
Bethesda, MD 20892, USA.
2 Cardiovascular Research Institute, University of California, San Francisco, CA
94143, USA.
* Authors for correspondence (e-mail: pao-tien.chuang{at}ucsf.edu; yingzi{at}mail.nih.gov)
Accepted 19 July 2006
Both the Wnt/ß-catenin and Ihh signaling pathways play essential roles in crucial aspects of endochondral ossification: osteoblast differentiation, chondrocyte proliferation and hypertrophy. To understand the genetic interaction between these two signaling pathways, we have inactivated the ß-catenin gene and upregulated Ihh signaling simultaneously in the same cells during endochondral skeletal development using ß-catenin and patched 1 floxed alleles. We uncovered previously unexpected roles of Ihh signaling in synovial joint formation and the essential function of Wnt/ß-catenin signaling in regulating chondrocyte survival. More importantly, we found that Wnt and Ihh signaling interact with each other in distinct ways to control osteoblast differentiation, chondrocyte proliferation, hypertrophy, survival and synovial joint formation in the developing endochondral bone. ß-catenin is required downstream of Ihh signaling and osterix expression for osteoblast differentiation. But in chondrocyte survival, ß-catenin is required upstream of Ihh signaling to inhibit chondrocyte apoptosis. In addition, Ihh signaling can inhibit chondrocyte hypertrophy and synovial joint formation independently of ß-catenin. However, there is a strong synergistic interaction between Wnt/ß-catenin and Ihh signaling in regulating synovial joint formation.
Key words: Wnt, ß-catenin, Ihh, Patched, Cartilage, Endochondral bone, Joint, Chondrocyte hypertrophy, Osteoblast differentiation
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Li and A. T. Dudley Noncanonical frizzled signaling regulates cell polarity of growth plate chondrocytes Development, April 1, 2009; 136(7): 1083 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nadanaka, M. Ishida, M. Ikegami, and H. Kitagawa Chondroitin 4-O-Sulfotransferase-1 Modulates Wnt-3a Signaling through Control of E Disaccharide Expression of Chondroitin Sulfate J. Biol. Chem., October 3, 2008; 283(40): 27333 - 27343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Grigoryan, P. Wend, A. Klaus, and W. Birchmeier Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of {beta}-catenin in mice Genes & Dev., September 1, 2008; 22(17): 2308 - 2341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Regard and Y. Yang Hedgehog Signaling in Postnatal Bone IBMS BoneKEy, July 1, 2008; 5(7): 243 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Sohaskey, J. Yu, M. A. Diaz, A. H. Plaas, and R. M. Harland JAWS coordinates chondrogenesis and synovial joint positioning Development, July 1, 2008; 135(13): 2215 - 2220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Mak, H. M. Kronenberg, P.-T. Chuang, S. Mackem, and Y. Yang Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy Development, June 1, 2008; 135(11): 1947 - 1956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. F. Day and Y. Yang Wnt and Hedgehog Signaling Pathways in Bone Development J. Bone Joint Surg. Am., February 1, 2008; 90(Supplement_1): 19 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Spagnoli, L. O'Rear, R. L. Chandler, F. Granero-Molto, D. P. Mortlock, A. E. Gorska, J. A. Weis, L. Longobardi, A. Chytil, K. Shimer, et al. TGF-{beta} signaling is essential for joint morphogenesis J. Cell Biol., July 30, 2007; 177(6): 1105 - 1117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Koyama, B. Young, M. Nagayama, Y. Shibukawa, M. Enomoto-Iwamoto, M. Iwamoto, Y. Maeda, B. Lanske, B. Song, R. Serra, et al. Conditional Kif3a ablation causes abnormal hedgehog signaling topography, growth plate dysfunction, and excessive bone and cartilage formation during mouse skeletogenesis Development, June 1, 2007; 134(11): 2159 - 2169. [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]
|
|
