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Identification and Characterization of a Novel Long Noncoding RNA that Regulates Osteogenesis in Diet-Induced Obesity Mice

As a precursor to type 2 diabetes mellitus (T2D), obesity adversely alters bone cell functions, causing decreased bone quality. Currently, the mechanisms leading to alterations in bone quality in obesity and subsequently T2D are largely unclear. Emerging evidence suggests that long noncoding RNAs (l...

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Autores principales: Hu, Zhekai, Qiu, Wei, Yu, Yuedi, Wu, Xingwen, Fang, Fuchun, Zhu, Xiaofang, Xu, Xiaoyang, Tu, Qisheng, Van Dyke, Thomas E., Morgan, Elise F., Chen, Jake
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068931/
https://www.ncbi.nlm.nih.gov/pubmed/35531098
http://dx.doi.org/10.3389/fcell.2022.832460
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author Hu, Zhekai
Qiu, Wei
Yu, Yuedi
Wu, Xingwen
Fang, Fuchun
Zhu, Xiaofang
Xu, Xiaoyang
Tu, Qisheng
Van Dyke, Thomas E.
Morgan, Elise F.
Chen, Jake
author_facet Hu, Zhekai
Qiu, Wei
Yu, Yuedi
Wu, Xingwen
Fang, Fuchun
Zhu, Xiaofang
Xu, Xiaoyang
Tu, Qisheng
Van Dyke, Thomas E.
Morgan, Elise F.
Chen, Jake
author_sort Hu, Zhekai
collection PubMed
description As a precursor to type 2 diabetes mellitus (T2D), obesity adversely alters bone cell functions, causing decreased bone quality. Currently, the mechanisms leading to alterations in bone quality in obesity and subsequently T2D are largely unclear. Emerging evidence suggests that long noncoding RNAs (lncRNAs) participate in a vast repertoire of biological processes and play essential roles in gene expression and posttranscriptional processes. Mechanistically, the expression of lncRNAs is implicated in pathogenesis surrounding the aggregation or alleviation of human diseases. To investigate the functional link between specific lncRNA and obesity-associated poor bone quality and elucidate the molecular mechanisms underlying the interaction between the two, we first assessed the structure of the bones in a diet-induced obese (DIO) mouse model. We found that bone microarchitecture markedly deteriorated in the DIO mice, mainly because of aberrant remodeling in the bone structure. The results of in vitro mechanistic experiments supported these observations. We then screened mRNAs and lncRNAs from DIO bones and functionally identified a specific lncRNA, Gm15222. Further analyses demonstrated that Gm15222 promotes osteogenesis and inhibits the expression of adipogenesis-related genes in DIO via recruitment of lysine demethylases KDM6B and KDM4B, respectively. Through this epigenetic pathway, Gm15222 modulates histone methylation of osteogenic genes. In addition, Gm15222 showed a positive correlation with the expression of a neighboring gene, BMP4. Together, the results of this study identified and provided initial characterization of Gm15222 as a critical epigenetic modifier that regulates osteogenesis and has potential roles in targeting the pathophysiology of bone disease in obesity and potential T2D.
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spelling pubmed-90689312022-05-05 Identification and Characterization of a Novel Long Noncoding RNA that Regulates Osteogenesis in Diet-Induced Obesity Mice Hu, Zhekai Qiu, Wei Yu, Yuedi Wu, Xingwen Fang, Fuchun Zhu, Xiaofang Xu, Xiaoyang Tu, Qisheng Van Dyke, Thomas E. Morgan, Elise F. Chen, Jake Front Cell Dev Biol Cell and Developmental Biology As a precursor to type 2 diabetes mellitus (T2D), obesity adversely alters bone cell functions, causing decreased bone quality. Currently, the mechanisms leading to alterations in bone quality in obesity and subsequently T2D are largely unclear. Emerging evidence suggests that long noncoding RNAs (lncRNAs) participate in a vast repertoire of biological processes and play essential roles in gene expression and posttranscriptional processes. Mechanistically, the expression of lncRNAs is implicated in pathogenesis surrounding the aggregation or alleviation of human diseases. To investigate the functional link between specific lncRNA and obesity-associated poor bone quality and elucidate the molecular mechanisms underlying the interaction between the two, we first assessed the structure of the bones in a diet-induced obese (DIO) mouse model. We found that bone microarchitecture markedly deteriorated in the DIO mice, mainly because of aberrant remodeling in the bone structure. The results of in vitro mechanistic experiments supported these observations. We then screened mRNAs and lncRNAs from DIO bones and functionally identified a specific lncRNA, Gm15222. Further analyses demonstrated that Gm15222 promotes osteogenesis and inhibits the expression of adipogenesis-related genes in DIO via recruitment of lysine demethylases KDM6B and KDM4B, respectively. Through this epigenetic pathway, Gm15222 modulates histone methylation of osteogenic genes. In addition, Gm15222 showed a positive correlation with the expression of a neighboring gene, BMP4. Together, the results of this study identified and provided initial characterization of Gm15222 as a critical epigenetic modifier that regulates osteogenesis and has potential roles in targeting the pathophysiology of bone disease in obesity and potential T2D. Frontiers Media S.A. 2022-04-21 /pmc/articles/PMC9068931/ /pubmed/35531098 http://dx.doi.org/10.3389/fcell.2022.832460 Text en Copyright © 2022 Hu, Qiu, Yu, Wu, Fang, Zhu, Xu, Tu, Van Dyke, Morgan and Chen. 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
Hu, Zhekai
Qiu, Wei
Yu, Yuedi
Wu, Xingwen
Fang, Fuchun
Zhu, Xiaofang
Xu, Xiaoyang
Tu, Qisheng
Van Dyke, Thomas E.
Morgan, Elise F.
Chen, Jake
Identification and Characterization of a Novel Long Noncoding RNA that Regulates Osteogenesis in Diet-Induced Obesity Mice
title Identification and Characterization of a Novel Long Noncoding RNA that Regulates Osteogenesis in Diet-Induced Obesity Mice
title_full Identification and Characterization of a Novel Long Noncoding RNA that Regulates Osteogenesis in Diet-Induced Obesity Mice
title_fullStr Identification and Characterization of a Novel Long Noncoding RNA that Regulates Osteogenesis in Diet-Induced Obesity Mice
title_full_unstemmed Identification and Characterization of a Novel Long Noncoding RNA that Regulates Osteogenesis in Diet-Induced Obesity Mice
title_short Identification and Characterization of a Novel Long Noncoding RNA that Regulates Osteogenesis in Diet-Induced Obesity Mice
title_sort identification and characterization of a novel long noncoding rna that regulates osteogenesis in diet-induced obesity mice
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068931/
https://www.ncbi.nlm.nih.gov/pubmed/35531098
http://dx.doi.org/10.3389/fcell.2022.832460
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