EBF2 regulates osteoblast-dependent differentiation of osteoclasts

Dev Cell. 2005 Dec;9(6):757-67. doi: 10.1016/j.devcel.2005.10.009.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Bone Development
  • Bone Resorption
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Differentiation*
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / physiology
  • Gene Expression Regulation
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • HeLa Cells
  • Homozygote
  • Humans
  • In Situ Hybridization
  • Lymphoid Enhancer-Binding Factor 1 / genetics
  • Lymphoid Enhancer-Binding Factor 1 / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Knockout
  • Osteoblasts / metabolism*
  • Osteoclasts / cytology*
  • Osteogenesis
  • Osteoprotegerin
  • Promoter Regions, Genetic / genetics
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism
  • Signal Transduction
  • T Cell Transcription Factor 1 / genetics
  • T Cell Transcription Factor 1 / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcriptional Activation
  • Wnt Proteins
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Carrier Proteins
  • Core Binding Factor Alpha 1 Subunit
  • Ebf2 protein, mouse
  • Glycoproteins
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Membrane Glycoproteins
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • Runx2 protein, mouse
  • T Cell Transcription Factor 1
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Tnfrsf11a protein, mouse
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Trans-Activators
  • Wnt Proteins
  • beta Catenin