Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment

Abstract We have previously shown that parathyroid hormone (PTH) induces the phosphorylation of the DNA-binding protein Nascent polypeptide associated complex And Coregulator alpha (NACA), leading to nuclear translocation of NACA and activation of target genes. Using ChIP-Seq against NACA in paralle...

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Autores principales:	Hadla Hariri, William N. Addison, René St-Arnaud
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aca8c110b41848c9aafc5fdb38ca2ccc
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spelling	oai:doaj.org-article:aca8c110b41848c9aafc5fdb38ca2ccc2021-12-02T18:27:49ZUbiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment10.1038/s41598-021-87608-x2045-2322https://doaj.org/article/aca8c110b41848c9aafc5fdb38ca2ccc2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87608-xhttps://doaj.org/toc/2045-2322Abstract We have previously shown that parathyroid hormone (PTH) induces the phosphorylation of the DNA-binding protein Nascent polypeptide associated complex And Coregulator alpha (NACA), leading to nuclear translocation of NACA and activation of target genes. Using ChIP-Seq against NACA in parallel with RNA-sequencing, we report the identification of Ubiquitin Specific Peptidase 53 (Usp53) as a target gene of PTH-activated NACA in osteoblasts. A binding site for NACA within the ChIP fragment from the Usp53 promoter was confirmed by electrophoretic mobility shift assay. Activity of the Usp53 promoter (− 2325/+ 238 bp) was regulated by the JUN-CREB complex and this activation relied on activated PKA and the presence of NACA. Usp53 knockdown in ST2 stromal cells stimulated expression of the osteoblastic markers Bglap2 (Osteocalcin) and Alpl (Alkaline phosphatase) and inhibited expression of the adipogenic markers Pparg and Cebpa. A similar effect was measured when knocking down Naca. During osteoblastogenesis, the impact of Usp53 knockdown on PTH responses varied depending on the maturation stage of the cells. In vivo implantation of Usp53-knockdown bone marrow stromal cells in immunocompromised mice showed an increase in osteoblast number and a decrease in adipocyte counts. Our data suggest that Usp53 modulates the fate of mesenchymal cells by impacting lineage selection.Hadla HaririWilliam N. AddisonRené St-ArnaudNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hadla Hariri William N. Addison René St-Arnaud Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment
description	Abstract We have previously shown that parathyroid hormone (PTH) induces the phosphorylation of the DNA-binding protein Nascent polypeptide associated complex And Coregulator alpha (NACA), leading to nuclear translocation of NACA and activation of target genes. Using ChIP-Seq against NACA in parallel with RNA-sequencing, we report the identification of Ubiquitin Specific Peptidase 53 (Usp53) as a target gene of PTH-activated NACA in osteoblasts. A binding site for NACA within the ChIP fragment from the Usp53 promoter was confirmed by electrophoretic mobility shift assay. Activity of the Usp53 promoter (− 2325/+ 238 bp) was regulated by the JUN-CREB complex and this activation relied on activated PKA and the presence of NACA. Usp53 knockdown in ST2 stromal cells stimulated expression of the osteoblastic markers Bglap2 (Osteocalcin) and Alpl (Alkaline phosphatase) and inhibited expression of the adipogenic markers Pparg and Cebpa. A similar effect was measured when knocking down Naca. During osteoblastogenesis, the impact of Usp53 knockdown on PTH responses varied depending on the maturation stage of the cells. In vivo implantation of Usp53-knockdown bone marrow stromal cells in immunocompromised mice showed an increase in osteoblast number and a decrease in adipocyte counts. Our data suggest that Usp53 modulates the fate of mesenchymal cells by impacting lineage selection.
format	article
author	Hadla Hariri William N. Addison René St-Arnaud
author_facet	Hadla Hariri William N. Addison René St-Arnaud
author_sort	Hadla Hariri
title	Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment
title_short	Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment
title_full	Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment
title_fullStr	Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment
title_full_unstemmed	Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment
title_sort	ubiquitin specific peptidase usp53 regulates osteoblast versus adipocyte lineage commitment
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/aca8c110b41848c9aafc5fdb38ca2ccc
work_keys_str_mv	AT hadlahariri ubiquitinspecificpeptidaseusp53regulatesosteoblastversusadipocytelineagecommitment AT williamnaddison ubiquitinspecificpeptidaseusp53regulatesosteoblastversusadipocytelineagecommitment AT renestarnaud ubiquitinspecificpeptidaseusp53regulatesosteoblastversusadipocytelineagecommitment
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Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment

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