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The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament
Ossification of the posterior longitudinal ligament (OPLL) presents as pathological heterotopic ossification of the spinal ligaments. However, its underlying molecular mechanism is still unclear. Our previous findings suggested that altered microRNA regulatory network are critical for the developmen...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003989/ https://www.ncbi.nlm.nih.gov/pubmed/29907859 http://dx.doi.org/10.1038/s41598-018-27514-x |
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author | Xu, Chen Zhang, Hao Gu, Wei Wu, Huiqiao Chen, Yuanyuan Zhou, Wenchao Sun, Baifeng Shen, Xiaolong Zhang, Zicheng Wang, Yue Liu, Yang Yuan, Wen |
author_facet | Xu, Chen Zhang, Hao Gu, Wei Wu, Huiqiao Chen, Yuanyuan Zhou, Wenchao Sun, Baifeng Shen, Xiaolong Zhang, Zicheng Wang, Yue Liu, Yang Yuan, Wen |
author_sort | Xu, Chen |
collection | PubMed |
description | Ossification of the posterior longitudinal ligament (OPLL) presents as pathological heterotopic ossification of the spinal ligaments. However, its underlying molecular mechanism is still unclear. Our previous findings suggested that altered microRNA regulatory network are critical for the development of OPLL. Here, we set out to unveiling the detailed mechanism of those altered OPLL-specific microRNAs. We screened a set of differentially expressed OPLL-specific microRNAs from the previous sequencing data and showed that microRNA-10a actively modulates the ossification of posterior ligament cells in vitro. Using a tissue-engineered scaffold grown from 4-week-old BALB/c homozygous nude mice, we found that altered microRNA-10a expression in posterior ligament cells indeed affected the heterotopic bone formation in vivo. Furthermore, computational analysis showed that the negative ossification regulator ID3 is a functional target gene of microRNA-10a, and its expression was also significantly altered during microRNA-10a modulation both in vitro and in vivo. Also, we have demonstrated that the ossification promoting function of microRNA-10a requires ID3, as ID3 actively inhibits RUNX2. Thus, we identified a critical role for highly altered OPLL-specific microRNA-10a in regulating the development of OPLL by modulating the ID3/RUNX2 axis. |
format | Online Article Text |
id | pubmed-6003989 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60039892018-06-26 The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament Xu, Chen Zhang, Hao Gu, Wei Wu, Huiqiao Chen, Yuanyuan Zhou, Wenchao Sun, Baifeng Shen, Xiaolong Zhang, Zicheng Wang, Yue Liu, Yang Yuan, Wen Sci Rep Article Ossification of the posterior longitudinal ligament (OPLL) presents as pathological heterotopic ossification of the spinal ligaments. However, its underlying molecular mechanism is still unclear. Our previous findings suggested that altered microRNA regulatory network are critical for the development of OPLL. Here, we set out to unveiling the detailed mechanism of those altered OPLL-specific microRNAs. We screened a set of differentially expressed OPLL-specific microRNAs from the previous sequencing data and showed that microRNA-10a actively modulates the ossification of posterior ligament cells in vitro. Using a tissue-engineered scaffold grown from 4-week-old BALB/c homozygous nude mice, we found that altered microRNA-10a expression in posterior ligament cells indeed affected the heterotopic bone formation in vivo. Furthermore, computational analysis showed that the negative ossification regulator ID3 is a functional target gene of microRNA-10a, and its expression was also significantly altered during microRNA-10a modulation both in vitro and in vivo. Also, we have demonstrated that the ossification promoting function of microRNA-10a requires ID3, as ID3 actively inhibits RUNX2. Thus, we identified a critical role for highly altered OPLL-specific microRNA-10a in regulating the development of OPLL by modulating the ID3/RUNX2 axis. Nature Publishing Group UK 2018-06-15 /pmc/articles/PMC6003989/ /pubmed/29907859 http://dx.doi.org/10.1038/s41598-018-27514-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Xu, Chen Zhang, Hao Gu, Wei Wu, Huiqiao Chen, Yuanyuan Zhou, Wenchao Sun, Baifeng Shen, Xiaolong Zhang, Zicheng Wang, Yue Liu, Yang Yuan, Wen The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament |
title | The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament |
title_full | The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament |
title_fullStr | The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament |
title_full_unstemmed | The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament |
title_short | The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament |
title_sort | microrna-10a/id3/runx2 axis modulates the development of ossification of posterior longitudinal ligament |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003989/ https://www.ncbi.nlm.nih.gov/pubmed/29907859 http://dx.doi.org/10.1038/s41598-018-27514-x |
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