EBF2 regulates osteoblast-dependent differentiation of osteoclasts.
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.
Kieslinger
Matthias
M
Gene center and Institute for Biochemistry, University of Munich, 81377 Munich, Germany.
Folberth
Stephanie
S
Dobreva
Gergana
G
Dorn
Tatjana
T
Croci
Laura
L
Erben
Reinhold
R
Consalez
G Giacomo
GG
Grosschedl
Rudolf
R
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D001846:Bone Development; D001862:Bone Resorption; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006720:Homozygote; D006801:Humans; D017403:In Situ Hybridization; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology*; D010012:Osteogenesis; D053244:Osteoprotegerin; D011401:Promoter Regions, Genetic / Q000235:genetics; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1 / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D051153:Wnt Proteins; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D006023:Glycoproteins; D051821:Lymphoid Enhancer-Binding Factor 1; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D051822:T Cell Transcription Factor 1; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin; C489922:Ebf2 protein, mouse; C497574:Lef1 protein, mouse; C493716:Runx2 protein, mouse; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse