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Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages.

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Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages. / Kiviranta, Riku; Yamana, Kei; Saito, Hiroaki; Ho, Daniel K; Laine, Julius; Tarkkonen, Kati; Nieminen-Pihala, Vappu; Hesse, Eric; Correa, Diego; Määttä, Jorma; Tessarollo, Lino; Rosen, Evan D; Horne, William C; Jenkins, Nancy A; Copeland, Neal G; Warming, Soren; Baron, Roland.

In: J EXP MED, Vol. 210, No. 5, 5, 2013, p. 969-985.

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

Harvard

Kiviranta, R, Yamana, K, Saito, H, Ho, DK, Laine, J, Tarkkonen, K, Nieminen-Pihala, V, Hesse, E, Correa, D, Määttä, J, Tessarollo, L, Rosen, ED, Horne, WC, Jenkins, NA, Copeland, NG, Warming, S & Baron, R 2013, 'Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages.', J EXP MED, vol. 210, no. 5, 5, pp. 969-985. <http://www.ncbi.nlm.nih.gov/pubmed/23569325?dopt=Citation>

APA

Kiviranta, R., Yamana, K., Saito, H., Ho, D. K., Laine, J., Tarkkonen, K., Nieminen-Pihala, V., Hesse, E., Correa, D., Määttä, J., Tessarollo, L., Rosen, E. D., Horne, W. C., Jenkins, N. A., Copeland, N. G., Warming, S., & Baron, R. (2013). Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages. J EXP MED, 210(5), 969-985. [5]. http://www.ncbi.nlm.nih.gov/pubmed/23569325?dopt=Citation

Vancouver

Kiviranta R, Yamana K, Saito H, Ho DK, Laine J, Tarkkonen K et al. Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages. J EXP MED. 2013;210(5):969-985. 5.

Bibtex

@article{8bfe87a569624220b8bed65542106cba,
title = "Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages.",
abstract = "Bone homeostasis is maintained by the coupled actions of hematopoietic bone-resorbing osteoclasts (OCs) and mesenchymal bone-forming osteoblasts (OBs). Here we identify early B cell factor 1 (Ebf1) and the transcriptional coregulator Zfp521 as components of the machinery that regulates bone homeostasis through coordinated effects in both lineages. Deletion of Zfp521 in OBs led to impaired bone formation and increased OB-dependent osteoclastogenesis (OC-genesis), and deletion in hematopoietic cells revealed a strong cell-autonomous role for Zfp521 in OC progenitors. In adult mice, the effects of Zfp521 were largely caused by repression of Ebf1, and the bone phenotype of Zfp521(+/-) mice was rescued in Zfp521(+/-):Ebf1(+/-) mice. Zfp521 interacted with Ebf1 and repressed its transcriptional activity. Accordingly, deletion of Zfp521 led to increased Ebf1 activity in OBs and OCs. In vivo, Ebf1 overexpression in OBs resulted in suppressed bone formation, similar to the phenotype seen after OB-targeted deletion of Zfp521. Conversely, Ebf1 deletion led to cell-autonomous defects in both OB-dependent and cell-intrinsic OC-genesis, a phenotype opposite to that of the Zfp521 knockout. Thus, we have identified the interplay between Zfp521 and Ebf1 as a novel rheostat for bone homeostasis.",
keywords = "Animals, Mice, Gene Deletion, Phenotype, Transcription, Genetic, Core Binding Factor Alpha 1 Subunit/metabolism, Transcription Factors/*metabolism, *Gene Expression Regulation, Haploinsufficiency, Osteogenesis, Up-Regulation/genetics, Osteoblasts/metabolism/pathology, Trans-Activators/*metabolism, Cell Lineage/*genetics, Osteoclasts/metabolism/pathology, Bone Diseases, Metabolic/metabolism/pathology/physiopathology, Bone Resorption/metabolism/pathology/physiopathology, Bone and Bones/metabolism/*pathology/physiopathology, Germ Cells/metabolism, Hematopoietic System/*pathology, Homeostasis/*genetics, Mesoderm/pathology, Animals, Mice, Gene Deletion, Phenotype, Transcription, Genetic, Core Binding Factor Alpha 1 Subunit/metabolism, Transcription Factors/*metabolism, *Gene Expression Regulation, Haploinsufficiency, Osteogenesis, Up-Regulation/genetics, Osteoblasts/metabolism/pathology, Trans-Activators/*metabolism, Cell Lineage/*genetics, Osteoclasts/metabolism/pathology, Bone Diseases, Metabolic/metabolism/pathology/physiopathology, Bone Resorption/metabolism/pathology/physiopathology, Bone and Bones/metabolism/*pathology/physiopathology, Germ Cells/metabolism, Hematopoietic System/*pathology, Homeostasis/*genetics, Mesoderm/pathology",
author = "Riku Kiviranta and Kei Yamana and Hiroaki Saito and Ho, {Daniel K} and Julius Laine and Kati Tarkkonen and Vappu Nieminen-Pihala and Eric Hesse and Diego Correa and Jorma M{\"a}{\"a}tt{\"a} and Lino Tessarollo and Rosen, {Evan D} and Horne, {William C} and Jenkins, {Nancy A} and Copeland, {Neal G} and Soren Warming and Roland Baron",
year = "2013",
language = "English",
volume = "210",
pages = "969--985",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "5",

}

RIS

TY - JOUR

T1 - Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages.

AU - Kiviranta, Riku

AU - Yamana, Kei

AU - Saito, Hiroaki

AU - Ho, Daniel K

AU - Laine, Julius

AU - Tarkkonen, Kati

AU - Nieminen-Pihala, Vappu

AU - Hesse, Eric

AU - Correa, Diego

AU - Määttä, Jorma

AU - Tessarollo, Lino

AU - Rosen, Evan D

AU - Horne, William C

AU - Jenkins, Nancy A

AU - Copeland, Neal G

AU - Warming, Soren

AU - Baron, Roland

PY - 2013

Y1 - 2013

N2 - Bone homeostasis is maintained by the coupled actions of hematopoietic bone-resorbing osteoclasts (OCs) and mesenchymal bone-forming osteoblasts (OBs). Here we identify early B cell factor 1 (Ebf1) and the transcriptional coregulator Zfp521 as components of the machinery that regulates bone homeostasis through coordinated effects in both lineages. Deletion of Zfp521 in OBs led to impaired bone formation and increased OB-dependent osteoclastogenesis (OC-genesis), and deletion in hematopoietic cells revealed a strong cell-autonomous role for Zfp521 in OC progenitors. In adult mice, the effects of Zfp521 were largely caused by repression of Ebf1, and the bone phenotype of Zfp521(+/-) mice was rescued in Zfp521(+/-):Ebf1(+/-) mice. Zfp521 interacted with Ebf1 and repressed its transcriptional activity. Accordingly, deletion of Zfp521 led to increased Ebf1 activity in OBs and OCs. In vivo, Ebf1 overexpression in OBs resulted in suppressed bone formation, similar to the phenotype seen after OB-targeted deletion of Zfp521. Conversely, Ebf1 deletion led to cell-autonomous defects in both OB-dependent and cell-intrinsic OC-genesis, a phenotype opposite to that of the Zfp521 knockout. Thus, we have identified the interplay between Zfp521 and Ebf1 as a novel rheostat for bone homeostasis.

AB - Bone homeostasis is maintained by the coupled actions of hematopoietic bone-resorbing osteoclasts (OCs) and mesenchymal bone-forming osteoblasts (OBs). Here we identify early B cell factor 1 (Ebf1) and the transcriptional coregulator Zfp521 as components of the machinery that regulates bone homeostasis through coordinated effects in both lineages. Deletion of Zfp521 in OBs led to impaired bone formation and increased OB-dependent osteoclastogenesis (OC-genesis), and deletion in hematopoietic cells revealed a strong cell-autonomous role for Zfp521 in OC progenitors. In adult mice, the effects of Zfp521 were largely caused by repression of Ebf1, and the bone phenotype of Zfp521(+/-) mice was rescued in Zfp521(+/-):Ebf1(+/-) mice. Zfp521 interacted with Ebf1 and repressed its transcriptional activity. Accordingly, deletion of Zfp521 led to increased Ebf1 activity in OBs and OCs. In vivo, Ebf1 overexpression in OBs resulted in suppressed bone formation, similar to the phenotype seen after OB-targeted deletion of Zfp521. Conversely, Ebf1 deletion led to cell-autonomous defects in both OB-dependent and cell-intrinsic OC-genesis, a phenotype opposite to that of the Zfp521 knockout. Thus, we have identified the interplay between Zfp521 and Ebf1 as a novel rheostat for bone homeostasis.

KW - Animals

KW - Mice

KW - Gene Deletion

KW - Phenotype

KW - Transcription, Genetic

KW - Core Binding Factor Alpha 1 Subunit/metabolism

KW - Transcription Factors/metabolism

KW - Gene Expression Regulation

KW - Haploinsufficiency

KW - Osteogenesis

KW - Up-Regulation/genetics

KW - Osteoblasts/metabolism/pathology

KW - Trans-Activators/metabolism

KW - Cell Lineage/genetics

KW - Osteoclasts/metabolism/pathology

KW - Bone Diseases, Metabolic/metabolism/pathology/physiopathology

KW - Bone Resorption/metabolism/pathology/physiopathology

KW - Bone and Bones/metabolism/pathology/physiopathology

KW - Germ Cells/metabolism

KW - Hematopoietic System/pathology

KW - Homeostasis/genetics

KW - Mesoderm/pathology

KW - Animals

KW - Mice

KW - Gene Deletion

KW - Phenotype

KW - Transcription, Genetic

KW - Core Binding Factor Alpha 1 Subunit/metabolism

KW - Transcription Factors/metabolism

KW - Gene Expression Regulation

KW - Haploinsufficiency

KW - Osteogenesis

KW - Up-Regulation/genetics

KW - Osteoblasts/metabolism/pathology

KW - Trans-Activators/metabolism

KW - Cell Lineage/genetics

KW - Osteoclasts/metabolism/pathology

KW - Bone Diseases, Metabolic/metabolism/pathology/physiopathology

KW - Bone Resorption/metabolism/pathology/physiopathology

KW - Bone and Bones/metabolism/pathology/physiopathology

KW - Germ Cells/metabolism

KW - Hematopoietic System/pathology

KW - Homeostasis/genetics

KW - Mesoderm/pathology

M3 - SCORING: Journal article

VL - 210

SP - 969

EP - 985

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 5

M1 - 5

ER -