Inhibition of β-catenin signaling causes defects in postnatal cartilage development

Mo Chen, Mei Zhu, Hani Awad, Tian Fang Li, Tzong Jen Sheu, Brendan F. Boyce, Di Chen, Regis J. O'Keefe

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

The Wnt/β-catenin signaling pathway is essential for normal skeletal development because conditional gain or loss of function of β-catenin in cartilage results in embryonic or early postnatal death. To address the role of β-catenin in postnatal skeletal growth and development, Col2al-ICAT transgenic mice were generated. Mice were viable and had normal size at birth, but became progressively runted. Transgene expression was limited to the chondrocytes in the growth plate and articular cartilages and was associated with decreased β-catenin signaling. Col2al-ICAT transgenic mice showed reduced chondrocyte proliferation and differentiation, and an increase in chondrocyte apoptosis, leading to decreased widths of the proliferating and hypertrophic zones, delayed formation of the secondary ossification center, and reduced skeletal growth. Isolated primary Col2al-ICAT transgenic chondrocytes showed reduced expression of chondrocyte genes associated with maturation, and demonstrated that VEGF gene expression requires cooperative interactions between BMP2 and β-catenin signaling. Altogether the findings confirm a crucial role for Wnt/ β-catenin in postnatal growth.

Original languageEnglish
Pages (from-to)1455-1465
Number of pages11
JournalJournal of cell science
Volume121
Issue number9
DOIs
StatePublished - May 1 2008
Externally publishedYes

Keywords

  • Chondrocyte
  • Endochondral bone formation
  • Inhibitor of β-catenin and TCF (ICAT)
  • Vascular endothelial growth factor (VEGF)
  • β-catenin

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    Chen, M., Zhu, M., Awad, H., Li, T. F., Sheu, T. J., Boyce, B. F., Chen, D., & O'Keefe, R. J. (2008). Inhibition of β-catenin signaling causes defects in postnatal cartilage development. Journal of cell science, 121(9), 1455-1465. https://doi.org/10.1242/jcs.020362