FoxA Family Members Are Crucial Regulators of the Hypertrophic Chondrocyte Differentiation Program

Andreia Ionescu, Elena Kozhemyakina, Claudia Nicolae, Klaus H. Kaestner, Bjorn R. Olsen, Andrew B. Lassar

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

During endochondral ossification, small, immature chondrocytes enlarge to form hypertrophic chondrocytes, which express collagen X. In this work, we demonstrate that FoxA factors are induced during chondrogenesis, bind to conserved binding sites in the collagen X enhancer, and can promote the expression of a collagen X-luciferase reporter in both chondrocytes and fibroblasts. In addition, we demonstrate by both gain- and loss-of-function analyses that FoxA factors play a crucial role in driving the expression of both endogenous collagen X and other hypertrophic chondrocyte-specific genes. Mice engineered to lack expression of both FoxA2 and FoxA3 in their chondrocytes display defects in chondrocyte hypertrophy, alkaline phosphatase expression, and mineralization in their sternebrae and, in addition, exhibit postnatal dwarfism that is coupled to significantly decreased expression of both collagen X and MMP13 in their growth plates. Our findings indicate that FoxA family members are crucial regulators of the hypertrophic chondrocyte differentiation program.

Original languageEnglish (US)
Pages (from-to)927-939
Number of pages13
JournalDevelopmental Cell
Volume22
Issue number5
DOIs
StatePublished - May 15 2012

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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