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

doi:10.1083/jcb.201009107

Back

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

Journal article

Open access

Peer reviewed

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, …

The Journal of cell biology, Vol.191(7), pp.1271-1283

2010-12-27

DOI: https://doi.org/10.1083/jcb.201009107

PMCID: PMC3010073

PMID: 21173110

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.

Files and links (1)

url

https://doi.org/10.1083/jcb.201009107View

Published (Version of record) Open

Metrics

5 Record Views

84 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.80 Bone Diseases; 1.80.766 Osteoclast
Web Of Science research areas: Cell Biology
ESI research areas: Molecular Biology & Genetics

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity
Creators: Eric Hesse - Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115
Hiroaki Saito - Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115
Riku Kiviranta - Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115
Diego Correa - Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115
Kei Yamana - Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, Teijin Pharma Limited, Teijin Institute for Biomedical Research, Hino, Tokyo 191-8512, Japan
Lynn Neff - Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115
Daniel Toben - Julius Wolff Institute and Center for Musculoskeletal Surgery and Berlin-Brandenburg Center for Regenerative Therapies, Charité University of Medicine Berlin, D-13353 Berlin, Germany, Julius Wolff Institute and Center for Musculoskeletal Surgery and Berlin-Brandenburg Center for Regenerative Therapies, Charité University of Medicine Berlin, D-13353 Berlin, Germany
Georg Duda - Julius Wolff Institute and Center for Musculoskeletal Surgery and Berlin-Brandenburg Center for Regenerative Therapies, Charité University of Medicine Berlin, D-13353 Berlin, Germany, Julius Wolff Institute and Center for Musculoskeletal Surgery and Berlin-Brandenburg Center for Regenerative Therapies, Charité University of Medicine Berlin, D-13353 Berlin, Germany
Azeddine Atfi - Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115
Valérie Geoffroy - Institut National de la Santé et de la Recherche Medicale U606, Université Paris Diderot-Paris 7, Hôpital Lariboisière, 75475 Paris, Cedex 10, France
William C Horne - Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115
Roland Baron - Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115, Department of Medicine, Harvard Medical School, and Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA 02115
Publication Details: The Journal of cell biology, Vol.191(7), pp.1271-1283
Academic Unit: UMMG Department of Orthopaedics
Language: English
Resource Type: Journal article
PMID: 21173110
PMCID: PMC3010073
Record Identifier: 991031599962202976