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A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection
BACKGROUND: Bone formation and loss are the characteristic clinical manifestations of leprosy, but the mechanisms underlying the bone remodeling with Mycobacterium leprae (M. leprae) infection are unclear. METHODOLOGY/PRINCIPAL FINDINGS: Osteocytes may have a role through regulating the differentiat...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098081/ https://www.ncbi.nlm.nih.gov/pubmed/35500036 http://dx.doi.org/10.1371/journal.pntd.0010379 |
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author | Gao, Zheng-Rong Liu, Qiong Zhao, Jie Zhao, Ya-Qiong Tan, Li Zhang, Shao-Hui Zhou, Ying-Hui Chen, Yun Guo, Yue Feng, Yun-Zhi |
author_facet | Gao, Zheng-Rong Liu, Qiong Zhao, Jie Zhao, Ya-Qiong Tan, Li Zhang, Shao-Hui Zhou, Ying-Hui Chen, Yun Guo, Yue Feng, Yun-Zhi |
author_sort | Gao, Zheng-Rong |
collection | PubMed |
description | BACKGROUND: Bone formation and loss are the characteristic clinical manifestations of leprosy, but the mechanisms underlying the bone remodeling with Mycobacterium leprae (M. leprae) infection are unclear. METHODOLOGY/PRINCIPAL FINDINGS: Osteocytes may have a role through regulating the differentiation of osteogenic lineages. To investigate osteocyte-related mechanisms in leprosy, we treated osteocyte-like cell with N-glycosylated muramyl dipeptide (N.g MDP). RNA-seq analysis showed 724 differentially expressed messenger RNAs (mRNAs) and 724 differentially expressed circular RNA (circRNAs). Of these, we filtered through eight osteogenic-related differentially expressed genes, according to the characteristic of competing endogenous RNA, PubMed databases, and bioinformatic analysis, including TargetScan, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. Based on these results, we built a circRNA–microRNA (miRNA)–mRNA triple network. Quantitative reverse-transcription polymerase chain reaction and western blots analyses confirmed decreased Clock expression in osteocyte-like cell, while increased in bone mesenchymal stem cells (BMSCs), implicating a crucial factor in osteogenic differentiation. Immunohistochemistry showed obviously increased expression of CLOCK protein in BMSCs and osteoblasts in N.g MDP–treated mice, but decreased expression in osteocytes. CONCLUSIONS/SIGNIFICANCE: This analytical method provided a basis for the relationship between N.g MDP and remodeling in osteocytes, and the circRNA–miRNA–mRNA triple network may offer a new target for leprosy therapeutics. |
format | Online Article Text |
id | pubmed-9098081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-90980812022-05-13 A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection Gao, Zheng-Rong Liu, Qiong Zhao, Jie Zhao, Ya-Qiong Tan, Li Zhang, Shao-Hui Zhou, Ying-Hui Chen, Yun Guo, Yue Feng, Yun-Zhi PLoS Negl Trop Dis Research Article BACKGROUND: Bone formation and loss are the characteristic clinical manifestations of leprosy, but the mechanisms underlying the bone remodeling with Mycobacterium leprae (M. leprae) infection are unclear. METHODOLOGY/PRINCIPAL FINDINGS: Osteocytes may have a role through regulating the differentiation of osteogenic lineages. To investigate osteocyte-related mechanisms in leprosy, we treated osteocyte-like cell with N-glycosylated muramyl dipeptide (N.g MDP). RNA-seq analysis showed 724 differentially expressed messenger RNAs (mRNAs) and 724 differentially expressed circular RNA (circRNAs). Of these, we filtered through eight osteogenic-related differentially expressed genes, according to the characteristic of competing endogenous RNA, PubMed databases, and bioinformatic analysis, including TargetScan, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. Based on these results, we built a circRNA–microRNA (miRNA)–mRNA triple network. Quantitative reverse-transcription polymerase chain reaction and western blots analyses confirmed decreased Clock expression in osteocyte-like cell, while increased in bone mesenchymal stem cells (BMSCs), implicating a crucial factor in osteogenic differentiation. Immunohistochemistry showed obviously increased expression of CLOCK protein in BMSCs and osteoblasts in N.g MDP–treated mice, but decreased expression in osteocytes. CONCLUSIONS/SIGNIFICANCE: This analytical method provided a basis for the relationship between N.g MDP and remodeling in osteocytes, and the circRNA–miRNA–mRNA triple network may offer a new target for leprosy therapeutics. Public Library of Science 2022-05-02 /pmc/articles/PMC9098081/ /pubmed/35500036 http://dx.doi.org/10.1371/journal.pntd.0010379 Text en © 2022 Gao et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gao, Zheng-Rong Liu, Qiong Zhao, Jie Zhao, Ya-Qiong Tan, Li Zhang, Shao-Hui Zhou, Ying-Hui Chen, Yun Guo, Yue Feng, Yun-Zhi A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection |
title | A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection |
title_full | A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection |
title_fullStr | A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection |
title_full_unstemmed | A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection |
title_short | A comprehensive analysis of the circRNA–miRNA–mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection |
title_sort | comprehensive analysis of the circrna–mirna–mrna network in osteocyte-like cell associated with mycobacterium leprae infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098081/ https://www.ncbi.nlm.nih.gov/pubmed/35500036 http://dx.doi.org/10.1371/journal.pntd.0010379 |
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