Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Chen, Zhang, Hao, Gu, Wei, Wu, Huiqiao, Chen, Yuanyuan, Zhou, Wenchao, Sun, Baifeng, Shen, Xiaolong, Zhang, Zicheng, Wang, Yue, Liu, Yang, Yuan, Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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
_version_ 1783332441792970752
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
work_keys_str_mv AT xuchen themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT zhanghao themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT guwei themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT wuhuiqiao themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT chenyuanyuan themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT zhouwenchao themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT sunbaifeng themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT shenxiaolong themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT zhangzicheng themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT wangyue themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT liuyang themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT yuanwen themicrorna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT xuchen microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT zhanghao microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT guwei microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT wuhuiqiao microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT chenyuanyuan microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT zhouwenchao microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT sunbaifeng microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT shenxiaolong microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT zhangzicheng microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT wangyue microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT liuyang microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament
AT yuanwen microrna10aid3runx2axismodulatesthedevelopmentofossificationofposteriorlongitudinalligament