Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs

<div><p>Osteoclasts are the sole bone resorbing cells, which undertake opposing roles to osteoblasts to affect skeletal mass and structure. However, unraveling the comprehensive molecular mechanisms behind osteoclast differentiation is necessitated to overcome limitations and scarcity of...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Salman M. Toor (8854751) (author)
مؤلفون آخرون: Sachin Wani (11704868) (author), Omar M. E. Albagha (11704871) (author)
منشور في: 2021
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author Salman M. Toor (8854751)
author2 Sachin Wani (11704868)
Omar M. E. Albagha (11704871)
author2_role author
author
author_facet Salman M. Toor (8854751)
Sachin Wani (11704868)
Omar M. E. Albagha (11704871)
author_role author
dc.creator.none.fl_str_mv Salman M. Toor (8854751)
Sachin Wani (11704868)
Omar M. E. Albagha (11704871)
dc.date.none.fl_str_mv 2021-11-15T03:00:00Z
dc.identifier.none.fl_str_mv 10.3389/fgene.2021.781272
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Comprehensive_Transcriptomic_Profiling_of_Murine_Osteoclast_Differentiation_Reveals_Novel_Differentially_Expressed_Genes_and_LncRNAs/25771563
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Biochemistry and cell biology
osteoclast
osteopororosis
bone resorption
RANK ligand (RANKL)
differentiation
dc.title.none.fl_str_mv Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>Osteoclasts are the sole bone resorbing cells, which undertake opposing roles to osteoblasts to affect skeletal mass and structure. However, unraveling the comprehensive molecular mechanisms behind osteoclast differentiation is necessitated to overcome limitations and scarcity of available data, particularly in relation with the emerging roles of long non-coding RNAs (LncRNAs) in gene expression. In this study, we performed comprehensive and progressive analyses of the dynamic transcriptomes of murine osteoclasts, generated in vitro. We compared the total RNA-based transcriptomes of murine bone marrow derived cells with differentiated osteoclasts, while focusing on potentially novel genes and LncRNAs, to uncover critical genes and their associated pathways, which are differentially regulated during osteoclast differentiation. We found 4,214 differentially regulated genes during osteoclast differentiation, which included various types of LncRNAs. Among the upregulated protein coding genes not previously associated with osteoclast are Pheta1, Hagh, Gfpt1 and Nol4, while downregulated genes included Plau, Ltf, Sell and Zfp831. Notably, we report Nol4 as a novel gene related to osteoclast activity since Nol4 knockout mice Nol4em1(International Mouse Phenotyping Consortium)J exhibit increased bone mineral density. Moreover, the differentially expressed LncRNAs included antisense and long intergenic non-coding RNAs, among others. Overall, immune-related and metabolism-related genes were downregulated, while anatomical morphogenesis and remodeling-related genes were upregulated in early-differentiated osteoclasts with sustained downregulation of immune-related genes in mature osteoclasts. The gene signatures and the comprehensive transcriptome of osteoclast differentiation provided herein can serve as an invaluable resource for deciphering gene dysregulation in osteoclast-related pathologic conditions.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Frontiers in Genetics<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fgene.2021.781272" target="_blank">https://dx.doi.org/10.3389/fgene.2021.781272</a></p>
eu_rights_str_mv openAccess
id Manara2_8301c488e1218c525b330ad8d04a20f9
identifier_str_mv 10.3389/fgene.2021.781272
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25771563
publishDate 2021
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spelling Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAsSalman M. Toor (8854751)Sachin Wani (11704868)Omar M. E. Albagha (11704871)Biological sciencesBiochemistry and cell biologyosteoclastosteopororosisbone resorptionRANK ligand (RANKL)differentiation<div><p>Osteoclasts are the sole bone resorbing cells, which undertake opposing roles to osteoblasts to affect skeletal mass and structure. However, unraveling the comprehensive molecular mechanisms behind osteoclast differentiation is necessitated to overcome limitations and scarcity of available data, particularly in relation with the emerging roles of long non-coding RNAs (LncRNAs) in gene expression. In this study, we performed comprehensive and progressive analyses of the dynamic transcriptomes of murine osteoclasts, generated in vitro. We compared the total RNA-based transcriptomes of murine bone marrow derived cells with differentiated osteoclasts, while focusing on potentially novel genes and LncRNAs, to uncover critical genes and their associated pathways, which are differentially regulated during osteoclast differentiation. We found 4,214 differentially regulated genes during osteoclast differentiation, which included various types of LncRNAs. Among the upregulated protein coding genes not previously associated with osteoclast are Pheta1, Hagh, Gfpt1 and Nol4, while downregulated genes included Plau, Ltf, Sell and Zfp831. Notably, we report Nol4 as a novel gene related to osteoclast activity since Nol4 knockout mice Nol4em1(International Mouse Phenotyping Consortium)J exhibit increased bone mineral density. Moreover, the differentially expressed LncRNAs included antisense and long intergenic non-coding RNAs, among others. Overall, immune-related and metabolism-related genes were downregulated, while anatomical morphogenesis and remodeling-related genes were upregulated in early-differentiated osteoclasts with sustained downregulation of immune-related genes in mature osteoclasts. The gene signatures and the comprehensive transcriptome of osteoclast differentiation provided herein can serve as an invaluable resource for deciphering gene dysregulation in osteoclast-related pathologic conditions.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Frontiers in Genetics<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fgene.2021.781272" target="_blank">https://dx.doi.org/10.3389/fgene.2021.781272</a></p>2021-11-15T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fgene.2021.781272https://figshare.com/articles/journal_contribution/Comprehensive_Transcriptomic_Profiling_of_Murine_Osteoclast_Differentiation_Reveals_Novel_Differentially_Expressed_Genes_and_LncRNAs/25771563CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/257715632021-11-15T03:00:00Z
spellingShingle Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs
Salman M. Toor (8854751)
Biological sciences
Biochemistry and cell biology
osteoclast
osteopororosis
bone resorption
RANK ligand (RANKL)
differentiation
status_str publishedVersion
title Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs
title_full Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs
title_fullStr Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs
title_full_unstemmed Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs
title_short Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs
title_sort Comprehensive Transcriptomic Profiling of Murine Osteoclast Differentiation Reveals Novel Differentially Expressed Genes and LncRNAs
topic Biological sciences
Biochemistry and cell biology
osteoclast
osteopororosis
bone resorption
RANK ligand (RANKL)
differentiation