Hdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via Pmepa1

Abstract Previous studies examining the role of the histone deacetylase Hdac3 within myeloid cells demonstrated that Hdac3 promotes M2 activation and tissue healing in inflammatory conditions. Since myeloid lineage cells are required for proper bone formation and regeneration, in this study we exami...

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Autores principales:	David H. H. Molstad, Elizabeth Zars, Andrew Norton, Kim C. Mansky, Jennifer J. Westendorf, Elizabeth W. Bradley
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/75c8d6bcd4f746f8a282c844bfc8dcbf
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spelling	oai:doaj.org-article:75c8d6bcd4f746f8a282c844bfc8dcbf2021-12-02T11:43:51ZHdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via Pmepa110.1038/s41598-020-78364-52045-2322https://doaj.org/article/75c8d6bcd4f746f8a282c844bfc8dcbf2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78364-5https://doaj.org/toc/2045-2322Abstract Previous studies examining the role of the histone deacetylase Hdac3 within myeloid cells demonstrated that Hdac3 promotes M2 activation and tissue healing in inflammatory conditions. Since myeloid lineage cells are required for proper bone formation and regeneration, in this study we examined the functions of Hdac3 during bone healing. Conditional deletion of Hdac3 within myeloid progenitors accelerates healing of cortical bone defects. Moreover, reduced osteoclast numbers within the defect site are correlated with Hdac3 suppression. Ex vivo osteoclastogenesis assays further demonstrate that Hdac3 deficiency limits osteoclastogenesis, the number of nuclei per cell and bone resorption, suggesting a defect in cell fusion. High throughput RNA sequencing identified the transmembrane protein Pmepa1 as a differentially expressed gene within osteoclast progenitor cells. Knockdown of Pmepa1 partially restores defects in osteoclastogenesis induced by Hdac3 deficiency. These results show that Hdac3 is required for optimal bone healing and osteoclast fusion, potentially via its regulation of Pmepa1 expression.David H. H. MolstadElizabeth ZarsAndrew NortonKim C. ManskyJennifer J. WestendorfElizabeth W. BradleyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David H. H. Molstad Elizabeth Zars Andrew Norton Kim C. Mansky Jennifer J. Westendorf Elizabeth W. Bradley Hdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via Pmepa1
description	Abstract Previous studies examining the role of the histone deacetylase Hdac3 within myeloid cells demonstrated that Hdac3 promotes M2 activation and tissue healing in inflammatory conditions. Since myeloid lineage cells are required for proper bone formation and regeneration, in this study we examined the functions of Hdac3 during bone healing. Conditional deletion of Hdac3 within myeloid progenitors accelerates healing of cortical bone defects. Moreover, reduced osteoclast numbers within the defect site are correlated with Hdac3 suppression. Ex vivo osteoclastogenesis assays further demonstrate that Hdac3 deficiency limits osteoclastogenesis, the number of nuclei per cell and bone resorption, suggesting a defect in cell fusion. High throughput RNA sequencing identified the transmembrane protein Pmepa1 as a differentially expressed gene within osteoclast progenitor cells. Knockdown of Pmepa1 partially restores defects in osteoclastogenesis induced by Hdac3 deficiency. These results show that Hdac3 is required for optimal bone healing and osteoclast fusion, potentially via its regulation of Pmepa1 expression.
format	article
author	David H. H. Molstad Elizabeth Zars Andrew Norton Kim C. Mansky Jennifer J. Westendorf Elizabeth W. Bradley
author_facet	David H. H. Molstad Elizabeth Zars Andrew Norton Kim C. Mansky Jennifer J. Westendorf Elizabeth W. Bradley
author_sort	David H. H. Molstad
title	Hdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via Pmepa1
title_short	Hdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via Pmepa1
title_full	Hdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via Pmepa1
title_fullStr	Hdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via Pmepa1
title_full_unstemmed	Hdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via Pmepa1
title_sort	hdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via pmepa1
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/75c8d6bcd4f746f8a282c844bfc8dcbf
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Hdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via Pmepa1

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