EBF2 Regulates Osteoblast-Dependent Differentiation of Osteoclasts
Copyright policy )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.
- University of Copenhagen Denmark
- University of Copenhagen Denmark
- Vita-Salute San Raffaele University Italy
- National Institute for Nuclear Physics Italy
- Ludwig-Maximilians-Universität München Germany
Lymphoid Enhancer-Binding Factor 1, Osteoclasts, Core Binding Factor Alpha 1 Subunit, General Biochemistry, Genetics and Molecular Biology, Mice, Osteogenesis, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Bone Resorption, Molecular Biology, In Situ Hybridization, Glycoproteins, Mice, Knockout, Bone Development, Membrane Glycoproteins, Osteoblasts, Homozygote, Cell Differentiation, Cell Biology, Gene Expression Regulation, Carrier Proteins, Developmental Biology, HeLa Cells
Lymphoid Enhancer-Binding Factor 1, Osteoclasts, Core Binding Factor Alpha 1 Subunit, General Biochemistry, Genetics and Molecular Biology, Mice, Osteogenesis, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Bone Resorption, Molecular Biology, In Situ Hybridization, Glycoproteins, Mice, Knockout, Bone Development, Membrane Glycoproteins, Osteoblasts, Homozygote, Cell Differentiation, Cell Biology, Gene Expression Regulation, Carrier Proteins, Developmental Biology, HeLa Cells
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