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Journal of Dental Research
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Biological

Wnt/β-catenin Signaling Regulates Cranial Base Development and Growth

M. Nagayama1,2, M. Iwamoto1, A. Hargett1, N. Kamiya3, Y. Tamamura1, B. Young1, T. Morrison1, H. Takeuchi2, M. Pacifici1, M. Enomoto-Iwamoto1 and E. Koyama1,*

1 Department of Orthopaedic Surgery, Thomas Jefferson University College of Medicine, Philadelphia, PA 19107, USA;
2 Department of Oral Pathology, Asahi University School of Dentistry, Mizuho, Gifu, 501-0296 Japan; and
3 Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA

Correspondence: * corresponding author, moto{at}dent.asahi-u.ac.jp, eiki.koyama{at}jefferson.edu

Wnt proteins and β-catenin signaling regulate major processes during embryonic development, and we hypothesized that they regulate cranial base synchondrosis development and growth. To address this issue, we analyzed cartilage-specific β-catenin-deficient mice. Mutant synchondroses lacked typical growth plate zones, and endochondral ossification was delayed. In reciprocal transgenic experiments, cartilage overexpression of a constitutive active Lef1, a transcriptional mediator of Wnt/β-catenin signaling, caused precocious chondrocyte hypertrophy and intermingling of immature and mature chondrocytes. The developmental changes seen in β-catenin-deficient synchondroses were accompanied by marked reductions in Ihh and PTHrP as well as sFRP-1, an endogenous Wnt signaling antagonist and a potential Ihh signaling target. Thus, Wnt/β-catenin signaling is essential for cranial base development and synchondrosis growth plate function. This pathway promotes chondrocyte maturation and ossification events, and may exert this important role by dampening the effects of Ihh-PTHrP together with sFRP-1.

Key Words: cranial base synchondrosis • Wnt/β-catenin • sFRP-1 • PTHrP • hedgehog signaling

Journal of Dental Research, Vol. 87, No. 3, 244-249 (2008)
DOI: 10.1177/154405910808700309
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