EBF2 regulates osteoblast-dependent differentiation of osteoclasts.

Research output: Contribution to journal › Journal article › Research › peer-review

  • Matthias Kieslinger
  • Stephanie Folberth
  • Gergana Dobreva
  • Tatjana Dorn
  • Laura Croci
  • Reinhold Erben
  • G Giacomo Consalez
  • Rudolf Grosschedl
Communication between bone-depositing osteoblasts and bone-resorbing osteoclasts is required for bone development and homeostasis. Here, we identify EBF2, a member of the early B cell factor (EBF) family of transcription factors that is expressed in osteoblast progenitors, as a regulator of osteoclast differentiation. We find that mice homozygous for a targeted inactivation of Ebf2 show reduced bone mass and an increase in the number of osteoclasts. These defects are accompanied by a marked downregulation of the osteoprotegerin (Opg) gene, encoding a RANK decoy receptor. EBF2 binds to sequences in the Opg promoter and transactivates the Opg promoter in synergy with the Wnt-responsive LEF1/TCF:beta-catenin pathway. Taken together, these data identify EBF2 as a regulator of RANK-RANKL signaling and osteoblast-dependent differentiation of osteoclasts.
Original languageEnglish
JournalDevelopmental Cell
Volume9
Issue number6
Pages (from-to)757-67
Number of pages10
ISSN1534-5807
DOIs
Publication statusPublished - 2005

Bibliographical note

Keywords: Animals; Basic Helix-Loop-Helix Transcription Factors; Bone Development; Bone Resorption; Carrier Proteins; Cell Differentiation; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation; Glycoproteins; Hela Cells; Homozygote; Humans; In Situ Hybridization; Lymphoid Enhancer-Binding Factor 1; Membrane Glycoproteins; Mice; Mice, Knockout; Osteoblasts; Osteoclasts; Osteogenesis; Osteoprotegerin; Promoter Regions (Genetics); RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Signal Transduction; T Cell Transcription Factor 1; Trans-Activation (Genetics); Trans-Activators; Wnt Proteins; beta Catenin

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