Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity.

Eric Hesse; Hiroaki Saito; Riku Kiviranta; Diego Correa; Kei Yamana; Lynn Neff; Daniel Toben; Georg Duda; Azeddine Atfi; Valérie Geoffroy; William C Horne; Roland Baron

Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity.

Standard

Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity. / Hesse, Eric; Saito, Hiroaki; Kiviranta, Riku; Correa, Diego; Yamana, Kei; Neff, Lynn; Toben, Daniel; Duda, Georg; Atfi, Azeddine; Geoffroy, Valérie; Horne, William C; Baron, Roland.

In: J CELL BIOL, Vol. 191, No. 7, 7, 2010, p. 1271-1283.

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

Harvard

Hesse, E, Saito, H, Kiviranta, R, Correa, D, Yamana, K, Neff, L, Toben, D, Duda, G, Atfi, A, Geoffroy, V, Horne, WC & Baron, R 2010, 'Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity.', J CELL BIOL, vol. 191, no. 7, 7, pp. 1271-1283. <http://www.ncbi.nlm.nih.gov/pubmed/21173110?dopt=Citation>

APA

Hesse, E., Saito, H., Kiviranta, R., Correa, D., Yamana, K., Neff, L., Toben, D., Duda, G., Atfi, A., Geoffroy, V., Horne, W. C., & Baron, R. (2010). Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity. J CELL BIOL, 191(7), 1271-1283. [7]. http://www.ncbi.nlm.nih.gov/pubmed/21173110?dopt=Citation

Vancouver

Hesse E, Saito H, Kiviranta R, Correa D, Yamana K, Neff L et al. Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity. J CELL BIOL. 2010;191(7):1271-1283. 7.

Bibtex

@article{90ebe1f192ca440fb7282a0510d486aa,

title = "Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity.",

abstract = "Runx2 is indispensable for osteoblast lineage commitment and early differentiation but also blocks osteoblast maturation, thereby causing bone loss in Runx2 transgenic mice. Zinc finger protein 521 (Zfp521) antagonizes Runx2 in vivo. Eliminating one Zfp521 allele mitigates the cleidocranial dysplasia-like phenotype of newborn Runx2(+/-) mice, whereas overexpressing Zfp521 exacerbates it. Overexpressing Zfp521 also reverses the severe osteopenia of adult Runx2 transgenic mice. Zfp521 binds to both Runx2 and histone deacetylase 3 (HDAC3), promotes their association, and antagonizes Runx2 transcriptional activity in an HDAC3-dependent manner. Mutating the Zfp521 zinc finger domains 6 and 26 reduces the binding of Zfp521 to Runx2 and inhibition of Runx2 activity. These data provide evidence that Zfp521 antagonizes Runx2 in vivo and thereby regulates two stages of osteoblast development, early during mesenchymal cell lineage commitment and later during osteoblast maturation. Thus, the balance and molecular interplay between Zfp521 and Runx2 contribute to the control of osteoblast differentiation, skeletal development, and bone homeostasis.",

keywords = "Animals, Mice, Rats, Heterozygote, Mice, Transgenic, Animals, Newborn, Cell Count, Mice, Inbred Strains, Alkaline Phosphatase/metabolism, Bone Development/*physiology, Bone Diseases, Metabolic/genetics/metabolism, Bone Remodeling/*physiology, Bone and Bones/abnormalities/embryology/metabolism/pathology, Calcification, Physiologic/genetics, Cell Differentiation/genetics, Core Binding Factor Alpha 1 Subunit/antagonists & inhibitors/genetics/*metabolism, DNA-Binding Proteins/genetics/*metabolism, Extracellular Matrix Proteins/genetics, Fractures, Spontaneous/genetics, Gene Expression/genetics, Histone Deacetylase Inhibitors/pharmacology, Histone Deacetylases/genetics/*metabolism, Mesenchymal Stem Cells/cytology, Osteoblasts/cytology/metabolism, Osteocalcin/genetics, Osteogenesis/*physiology, Osteopontin/genetics, Osteoprotegerin/genetics, Protein Binding/physiology, Protein Interaction Domains and Motifs/physiology, RANK Ligand/genetics, Response Elements/physiology, Transcription Factors/*genetics, Transcription, Genetic/drug effects/genetics, Zinc Fingers/physiology, Animals, Mice, Rats, Heterozygote, Mice, Transgenic, Animals, Newborn, Cell Count, Mice, Inbred Strains, Alkaline Phosphatase/metabolism, Bone Development/*physiology, Bone Diseases, Metabolic/genetics/metabolism, Bone Remodeling/*physiology, Bone and Bones/abnormalities/embryology/metabolism/pathology, Calcification, Physiologic/genetics, Cell Differentiation/genetics, Core Binding Factor Alpha 1 Subunit/antagonists & inhibitors/genetics/*metabolism, DNA-Binding Proteins/genetics/*metabolism, Extracellular Matrix Proteins/genetics, Fractures, Spontaneous/genetics, Gene Expression/genetics, Histone Deacetylase Inhibitors/pharmacology, Histone Deacetylases/genetics/*metabolism, Mesenchymal Stem Cells/cytology, Osteoblasts/cytology/metabolism, Osteocalcin/genetics, Osteogenesis/*physiology, Osteopontin/genetics, Osteoprotegerin/genetics, Protein Binding/physiology, Protein Interaction Domains and Motifs/physiology, RANK Ligand/genetics, Response Elements/physiology, Transcription Factors/*genetics, Transcription, Genetic/drug effects/genetics, Zinc Fingers/physiology",

author = "Eric Hesse and Hiroaki Saito and Riku Kiviranta and Diego Correa and Kei Yamana and Lynn Neff and Daniel Toben and Georg Duda and Azeddine Atfi and Val{\'e}rie Geoffroy and Horne, {William C} and Roland Baron",

year = "2010",

language = "English",

volume = "191",

pages = "1271--1283",

journal = "J CELL BIOL",

issn = "0021-9525",

publisher = "Rockefeller University Press",

number = "7",

}

RIS

TY - JOUR

T1 - Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity.

AU - Hesse, Eric

AU - Saito, Hiroaki

AU - Kiviranta, Riku

AU - Correa, Diego

AU - Yamana, Kei

AU - Neff, Lynn

AU - Toben, Daniel

AU - Duda, Georg

AU - Atfi, Azeddine

AU - Geoffroy, Valérie

AU - Horne, William C

AU - Baron, Roland

PY - 2010

Y1 - 2010

N2 - Runx2 is indispensable for osteoblast lineage commitment and early differentiation but also blocks osteoblast maturation, thereby causing bone loss in Runx2 transgenic mice. Zinc finger protein 521 (Zfp521) antagonizes Runx2 in vivo. Eliminating one Zfp521 allele mitigates the cleidocranial dysplasia-like phenotype of newborn Runx2(+/-) mice, whereas overexpressing Zfp521 exacerbates it. Overexpressing Zfp521 also reverses the severe osteopenia of adult Runx2 transgenic mice. Zfp521 binds to both Runx2 and histone deacetylase 3 (HDAC3), promotes their association, and antagonizes Runx2 transcriptional activity in an HDAC3-dependent manner. Mutating the Zfp521 zinc finger domains 6 and 26 reduces the binding of Zfp521 to Runx2 and inhibition of Runx2 activity. These data provide evidence that Zfp521 antagonizes Runx2 in vivo and thereby regulates two stages of osteoblast development, early during mesenchymal cell lineage commitment and later during osteoblast maturation. Thus, the balance and molecular interplay between Zfp521 and Runx2 contribute to the control of osteoblast differentiation, skeletal development, and bone homeostasis.

AB - Runx2 is indispensable for osteoblast lineage commitment and early differentiation but also blocks osteoblast maturation, thereby causing bone loss in Runx2 transgenic mice. Zinc finger protein 521 (Zfp521) antagonizes Runx2 in vivo. Eliminating one Zfp521 allele mitigates the cleidocranial dysplasia-like phenotype of newborn Runx2(+/-) mice, whereas overexpressing Zfp521 exacerbates it. Overexpressing Zfp521 also reverses the severe osteopenia of adult Runx2 transgenic mice. Zfp521 binds to both Runx2 and histone deacetylase 3 (HDAC3), promotes their association, and antagonizes Runx2 transcriptional activity in an HDAC3-dependent manner. Mutating the Zfp521 zinc finger domains 6 and 26 reduces the binding of Zfp521 to Runx2 and inhibition of Runx2 activity. These data provide evidence that Zfp521 antagonizes Runx2 in vivo and thereby regulates two stages of osteoblast development, early during mesenchymal cell lineage commitment and later during osteoblast maturation. Thus, the balance and molecular interplay between Zfp521 and Runx2 contribute to the control of osteoblast differentiation, skeletal development, and bone homeostasis.

KW - Animals

KW - Mice

KW - Rats

KW - Heterozygote

KW - Mice, Transgenic

KW - Animals, Newborn

KW - Cell Count

KW - Mice, Inbred Strains

KW - Alkaline Phosphatase/metabolism

KW - Bone Development/physiology

KW - Bone Diseases, Metabolic/genetics/metabolism

KW - Bone Remodeling/physiology

KW - Bone and Bones/abnormalities/embryology/metabolism/pathology

KW - Calcification, Physiologic/genetics

KW - Cell Differentiation/genetics

KW - Core Binding Factor Alpha 1 Subunit/antagonists & inhibitors/genetics/metabolism

KW - DNA-Binding Proteins/genetics/metabolism

KW - Extracellular Matrix Proteins/genetics

KW - Fractures, Spontaneous/genetics

KW - Gene Expression/genetics

KW - Histone Deacetylase Inhibitors/pharmacology

KW - Histone Deacetylases/genetics/metabolism

KW - Mesenchymal Stem Cells/cytology

KW - Osteoblasts/cytology/metabolism

KW - Osteocalcin/genetics

KW - Osteogenesis/physiology

KW - Osteopontin/genetics

KW - Osteoprotegerin/genetics

KW - Protein Binding/physiology

KW - Protein Interaction Domains and Motifs/physiology

KW - RANK Ligand/genetics

KW - Response Elements/physiology

KW - Transcription Factors/genetics

KW - Transcription, Genetic/drug effects/genetics

KW - Zinc Fingers/physiology