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Mechanisms of estrogen deficiency-induced osteoporosis based on transcriptome and DNA methylation

Osteoporosis is a disease that impacts the elderly. Low estrogen is related to changes in DNA methylation and consequent alterations in gene expression, leading to a new direction in research related to the pathophysiology of osteoporosis. We constructed an Ovariectomized (OVX) mouse model in our st...

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Autores principales: Xu, Ziying, Yu, Zihui, Chen, Ming, Zhang, Mingming, Chen, Ruijing, Yu, Haikuan, Lin, Yuan, Wang, Duanyang, Li, Shang, Huang, Ling, Li, Yi, Yuan, Jing, Yin, Pengbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618684/
https://www.ncbi.nlm.nih.gov/pubmed/36325359
http://dx.doi.org/10.3389/fcell.2022.1011725
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author Xu, Ziying
Yu, Zihui
Chen, Ming
Zhang, Mingming
Chen, Ruijing
Yu, Haikuan
Lin, Yuan
Wang, Duanyang
Li, Shang
Huang, Ling
Li, Yi
Yuan, Jing
Yin, Pengbin
author_facet Xu, Ziying
Yu, Zihui
Chen, Ming
Zhang, Mingming
Chen, Ruijing
Yu, Haikuan
Lin, Yuan
Wang, Duanyang
Li, Shang
Huang, Ling
Li, Yi
Yuan, Jing
Yin, Pengbin
author_sort Xu, Ziying
collection PubMed
description Osteoporosis is a disease that impacts the elderly. Low estrogen is related to changes in DNA methylation and consequent alterations in gene expression, leading to a new direction in research related to the pathophysiology of osteoporosis. We constructed an Ovariectomized (OVX) mouse model in our study, and the mouse models had osteoporosis based on the phenotype and methylation levels in the mouse’s bone. Furthermore, the methylation level of the OVX mice was significantly changed compared to that of SHAM mice. Therefore, we performed genome-level analysis on the mouse model using transcriptome and Whole Genome Bisulfite Sequencing (WGBS) by combining the data of two omics and discovered that the changes in gene expression level caused by osteoporosis primarily focused on the decrease of bone and muscle development and the activation of the immune system. According to intersection analysis of methylation and transcriptome data, the differentially expressed genes and pathways are consistent with the differentially expressed methylation locations and regions. Further, the differentially expressed methylation sites were mainly concentrated in promoters, exons, and other critical functional regions of essential differentially expressed genes. This is also the primary cause of gene differential expression variations, indicating that estrogen deficiency might regulate gene expression by altering methylation modification, leading to osteoporosis. We demonstrated the clinical value of methylation modification research, and these findings would improve the current understanding of underlying molecular mechanisms of osteoporosis incidence and development and provide new ideas for early detection and treatment of osteoporosis.
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spelling pubmed-96186842022-11-01 Mechanisms of estrogen deficiency-induced osteoporosis based on transcriptome and DNA methylation Xu, Ziying Yu, Zihui Chen, Ming Zhang, Mingming Chen, Ruijing Yu, Haikuan Lin, Yuan Wang, Duanyang Li, Shang Huang, Ling Li, Yi Yuan, Jing Yin, Pengbin Front Cell Dev Biol Cell and Developmental Biology Osteoporosis is a disease that impacts the elderly. Low estrogen is related to changes in DNA methylation and consequent alterations in gene expression, leading to a new direction in research related to the pathophysiology of osteoporosis. We constructed an Ovariectomized (OVX) mouse model in our study, and the mouse models had osteoporosis based on the phenotype and methylation levels in the mouse’s bone. Furthermore, the methylation level of the OVX mice was significantly changed compared to that of SHAM mice. Therefore, we performed genome-level analysis on the mouse model using transcriptome and Whole Genome Bisulfite Sequencing (WGBS) by combining the data of two omics and discovered that the changes in gene expression level caused by osteoporosis primarily focused on the decrease of bone and muscle development and the activation of the immune system. According to intersection analysis of methylation and transcriptome data, the differentially expressed genes and pathways are consistent with the differentially expressed methylation locations and regions. Further, the differentially expressed methylation sites were mainly concentrated in promoters, exons, and other critical functional regions of essential differentially expressed genes. This is also the primary cause of gene differential expression variations, indicating that estrogen deficiency might regulate gene expression by altering methylation modification, leading to osteoporosis. We demonstrated the clinical value of methylation modification research, and these findings would improve the current understanding of underlying molecular mechanisms of osteoporosis incidence and development and provide new ideas for early detection and treatment of osteoporosis. Frontiers Media S.A. 2022-10-17 /pmc/articles/PMC9618684/ /pubmed/36325359 http://dx.doi.org/10.3389/fcell.2022.1011725 Text en Copyright © 2022 Xu, Yu, Chen, Zhang, Chen, Yu, Lin, Wang, Li, Huang, Li, Yuan and Yin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Xu, Ziying
Yu, Zihui
Chen, Ming
Zhang, Mingming
Chen, Ruijing
Yu, Haikuan
Lin, Yuan
Wang, Duanyang
Li, Shang
Huang, Ling
Li, Yi
Yuan, Jing
Yin, Pengbin
Mechanisms of estrogen deficiency-induced osteoporosis based on transcriptome and DNA methylation
title Mechanisms of estrogen deficiency-induced osteoporosis based on transcriptome and DNA methylation
title_full Mechanisms of estrogen deficiency-induced osteoporosis based on transcriptome and DNA methylation
title_fullStr Mechanisms of estrogen deficiency-induced osteoporosis based on transcriptome and DNA methylation
title_full_unstemmed Mechanisms of estrogen deficiency-induced osteoporosis based on transcriptome and DNA methylation
title_short Mechanisms of estrogen deficiency-induced osteoporosis based on transcriptome and DNA methylation
title_sort mechanisms of estrogen deficiency-induced osteoporosis based on transcriptome and dna methylation
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618684/
https://www.ncbi.nlm.nih.gov/pubmed/36325359
http://dx.doi.org/10.3389/fcell.2022.1011725
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