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LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage

BACKGROUND: Cartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/β-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition,...

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Autores principales: Zhou, Wei, He, Xiaojuan, Chen, Ziyi, Fan, Danping, Wang, Yonghua, Feng, Hui, Zhang, Ge, Lu, Aiping, Xiao, Lianbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670131/
https://www.ncbi.nlm.nih.gov/pubmed/31366320
http://dx.doi.org/10.1186/s12859-019-2981-4
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author Zhou, Wei
He, Xiaojuan
Chen, Ziyi
Fan, Danping
Wang, Yonghua
Feng, Hui
Zhang, Ge
Lu, Aiping
Xiao, Lianbo
author_facet Zhou, Wei
He, Xiaojuan
Chen, Ziyi
Fan, Danping
Wang, Yonghua
Feng, Hui
Zhang, Ge
Lu, Aiping
Xiao, Lianbo
author_sort Zhou, Wei
collection PubMed
description BACKGROUND: Cartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/β-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally documented that lncRNA (long non-coding RNA) HOTAIR plays a key role in the regulation of Wnt/β-catenin pathway based on directly decreased WIF-1 expression. Further, it is reported that Wnt/β-catenin pathway is a potent pathway to regulate the expression of MMP-13, which is responsible for degradation of collagen type II in articular cartilage. It is increasingly recognized that systems modeling approach provides an opportunity to understand the complex relationships and direct quantitative analysis of dynamic network in various diseases. RESULTS: A dynamic network of lncRNA HOTAIR-mediated Wnt/β-catenin pathway regulating MMP-13 is developed to investigate the dynamic mechanism of the network involved in the pathogenesis of cartilage damage. Based on the network modeling, the potential therapeutic intervention point Axin is predicted and confirmed by the experimental validation. CONCLUSIONS: Our study provides a promising strategy for revealing potential dynamic mechanism and assessing potential targets which contribute to the prevention of the pathological conditions related to cartilage damage.
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spelling pubmed-66701312019-08-06 LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage Zhou, Wei He, Xiaojuan Chen, Ziyi Fan, Danping Wang, Yonghua Feng, Hui Zhang, Ge Lu, Aiping Xiao, Lianbo BMC Bioinformatics Research Article BACKGROUND: Cartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/β-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally documented that lncRNA (long non-coding RNA) HOTAIR plays a key role in the regulation of Wnt/β-catenin pathway based on directly decreased WIF-1 expression. Further, it is reported that Wnt/β-catenin pathway is a potent pathway to regulate the expression of MMP-13, which is responsible for degradation of collagen type II in articular cartilage. It is increasingly recognized that systems modeling approach provides an opportunity to understand the complex relationships and direct quantitative analysis of dynamic network in various diseases. RESULTS: A dynamic network of lncRNA HOTAIR-mediated Wnt/β-catenin pathway regulating MMP-13 is developed to investigate the dynamic mechanism of the network involved in the pathogenesis of cartilage damage. Based on the network modeling, the potential therapeutic intervention point Axin is predicted and confirmed by the experimental validation. CONCLUSIONS: Our study provides a promising strategy for revealing potential dynamic mechanism and assessing potential targets which contribute to the prevention of the pathological conditions related to cartilage damage. BioMed Central 2019-07-31 /pmc/articles/PMC6670131/ /pubmed/31366320 http://dx.doi.org/10.1186/s12859-019-2981-4 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhou, Wei
He, Xiaojuan
Chen, Ziyi
Fan, Danping
Wang, Yonghua
Feng, Hui
Zhang, Ge
Lu, Aiping
Xiao, Lianbo
LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage
title LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage
title_full LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage
title_fullStr LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage
title_full_unstemmed LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage
title_short LncRNA HOTAIR-mediated Wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage
title_sort lncrna hotair-mediated wnt/β-catenin network modeling to predict and validate therapeutic targets for cartilage damage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670131/
https://www.ncbi.nlm.nih.gov/pubmed/31366320
http://dx.doi.org/10.1186/s12859-019-2981-4
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