EBF2 regulates osteoblast-dependent differentiation of osteoclasts

Matthias Kieslinger; Stephanie Folberth; Gergana Dobreva; Tatjana Dorn; Laura Croci; Reinhold Erben; G. Giacomo Consalez; Rudolf Grosschedl

doi:10.1016/j.devcel.2005.10.009

EBF2 regulates osteoblast-dependent differentiation of osteoclasts

Matthias Kieslinger, Stephanie Folberth, Gergana Dobreva, Tatjana Dorn, Laura Croci, Reinhold Erben, G. Giacomo Consalez, Rudolf Grosschedl

IRCCS Ospedale San Raffaele

Research output: Contribution to journal › Article › peer-review

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:β-catenin pathway. Taken together, these data identify EBF2 as a regulator of RANK-RANKL signaling and osteoblast-dependent differentiation of osteoclasts.

Original language	English
Pages (from-to)	757-767
Number of pages	11
Journal	Developmental Cell
Volume	9
Issue number	6
DOIs	https://doi.org/10.1016/j.devcel.2005.10.009
Publication status	Published - Dec 2005

ASJC Scopus subject areas

Developmental Biology

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title = "EBF2 regulates osteoblast-dependent differentiation of osteoclasts",

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:β-catenin pathway. Taken together, these data identify EBF2 as a regulator of RANK-RANKL signaling and osteoblast-dependent differentiation of osteoclasts.",

author = "Matthias Kieslinger and Stephanie Folberth and Gergana Dobreva and Tatjana Dorn and Laura Croci and Reinhold Erben and Consalez, {G. Giacomo} and Rudolf Grosschedl",

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T1 - EBF2 regulates osteoblast-dependent differentiation of osteoclasts

AU - Kieslinger, Matthias

AU - Folberth, Stephanie

AU - Dobreva, Gergana

AU - Dorn, Tatjana

AU - Croci, Laura

AU - Erben, Reinhold

AU - Consalez, G. Giacomo

AU - Grosschedl, Rudolf

PY - 2005/12

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N2 - 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:β-catenin pathway. Taken together, these data identify EBF2 as a regulator of RANK-RANKL signaling and osteoblast-dependent differentiation of osteoclasts.

AB - 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:β-catenin pathway. Taken together, these data identify EBF2 as a regulator of RANK-RANKL signaling and osteoblast-dependent differentiation of osteoclasts.

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