Impaired mesenchymal stem cell differentiation and osteoclastogenesis in mice deficient for Igf2-P2 transcripts

Sylvie Nathalie Hardouin, Ruolin Guo, Paul Henri Romeo, Andras Nagy, Jane E. Aubin

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

Abstract

During embryonic development, Igf2 gene transcription is highly regulated through the use of several promoters whose specific roles are not defined. Here, we show that loss-of-function of one of these promoters, Igf2-P2, results in growth defects that are temporally and quantitatively different from those seen in Igf2-null mutants. In particular, Igf2-P2 mutants exhibit skeletal abnormalities characterized by thin and short bones with reduced mineralization and medullar cavity and with altered bone remodeling. These abnormalities are associated with decreased numbers of embryonic mesenchymal chondroprogenitors, adult mesenchymal stem cells and osteoprogenitors. Differentiation of osteoprogenitors into osteoblasts is impaired in the Igf2-P2 mutant mice in a cell-autonomous manner, and osteopontin is a target of the IGF2 signaling pathway during this differentiation. Igf2-P2 mutant mice also display impaired formation of giant osteoclasts owing to a defective micro-environment. These results support a model wherein transcriptional activity of the Igf2-P2 promoter regulates the fate of mesenchymal progenitors during bone development and remodeling in the adult, and regulates osteogenesis in a cell-autonomous and non-autonomous manner.

Original languageEnglish
Pages (from-to)203-213
Number of pages11
JournalDevelopment
Volume138
Issue number2
DOIs
Publication statusPublished - 15 Jan 2011
Externally publishedYes

Keywords

  • Igf2
  • Mesenchymal stem cells
  • Mouse
  • Osteogenesis
  • Progenitors
  • Stromal environment

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