Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment

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 RN...

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Autores principales: Hariri, Hadla, Addison, William N., St-Arnaud, René
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055676/
https://www.ncbi.nlm.nih.gov/pubmed/33875709
http://dx.doi.org/10.1038/s41598-021-87608-x
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author Hariri, Hadla
Addison, William N.
St-Arnaud, René
author_facet Hariri, Hadla
Addison, William N.
St-Arnaud, René
author_sort Hariri, Hadla
collection PubMed
description 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.
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spelling pubmed-80556762021-04-22 Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment Hariri, Hadla Addison, William N. St-Arnaud, René Sci Rep Article 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. Nature Publishing Group UK 2021-04-19 /pmc/articles/PMC8055676/ /pubmed/33875709 http://dx.doi.org/10.1038/s41598-021-87608-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hariri, Hadla
Addison, William N.
St-Arnaud, René
Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment
title 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_short Ubiquitin specific peptidase Usp53 regulates osteoblast versus adipocyte lineage commitment
title_sort ubiquitin specific peptidase usp53 regulates osteoblast versus adipocyte lineage commitment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055676/
https://www.ncbi.nlm.nih.gov/pubmed/33875709
http://dx.doi.org/10.1038/s41598-021-87608-x
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