Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.

Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control o...

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Autores principales: David F Razidlo, Tiffany J Whitney, Michelle E Casper, Meghan E McGee-Lawrence, Bridget A Stensgard, Xiaodong Li, Frank J Secreto, Sarah K Knutson, Scott W Hiebert, Jennifer J Westendorf
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Publicado: Public Library of Science (PLoS) 2010
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Acceso en línea:https://doaj.org/article/782d7d2bcd6441dc8442d80bda9aaaf9
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spelling oai:doaj.org-article:782d7d2bcd6441dc8442d80bda9aaaf92021-12-02T20:20:13ZHistone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.1932-620310.1371/journal.pone.0011492https://doaj.org/article/782d7d2bcd6441dc8442d80bda9aaaf92010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20628553/?tool=EBIhttps://doaj.org/toc/1932-6203Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO) mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health.David F RazidloTiffany J WhitneyMichelle E CasperMeghan E McGee-LawrenceBridget A StensgardXiaodong LiFrank J SecretoSarah K KnutsonScott W HiebertJennifer J WestendorfPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11492 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
David F Razidlo
Tiffany J Whitney
Michelle E Casper
Meghan E McGee-Lawrence
Bridget A Stensgard
Xiaodong Li
Frank J Secreto
Sarah K Knutson
Scott W Hiebert
Jennifer J Westendorf
Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.
description Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO) mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health.
format article
author David F Razidlo
Tiffany J Whitney
Michelle E Casper
Meghan E McGee-Lawrence
Bridget A Stensgard
Xiaodong Li
Frank J Secreto
Sarah K Knutson
Scott W Hiebert
Jennifer J Westendorf
author_facet David F Razidlo
Tiffany J Whitney
Michelle E Casper
Meghan E McGee-Lawrence
Bridget A Stensgard
Xiaodong Li
Frank J Secreto
Sarah K Knutson
Scott W Hiebert
Jennifer J Westendorf
author_sort David F Razidlo
title Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.
title_short Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.
title_full Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.
title_fullStr Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.
title_full_unstemmed Histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.
title_sort histone deacetylase 3 depletion in osteo/chondroprogenitor cells decreases bone density and increases marrow fat.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/782d7d2bcd6441dc8442d80bda9aaaf9
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