MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression

Abstract Distraction osteogenesis (DO) is a unique technique for promoting bone formation in clinical practice. However the underlying mechanism remains elusive. As epigenetic mediators, microRNAs have been reported to play important roles in regulating osteogenesis. In this study, after successfull...

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Autores principales: Yuxin Sun, Jia Xu, Liangliang Xu, Jinfang Zhang, Kaiming Chan, Xiaohua Pan, Gang Li
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/043522b641d740558735693d5fad70a1
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spelling oai:doaj.org-article:043522b641d740558735693d5fad70a12021-12-02T16:07:59ZMiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression10.1038/s41598-017-00466-42045-2322https://doaj.org/article/043522b641d740558735693d5fad70a12017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00466-4https://doaj.org/toc/2045-2322Abstract Distraction osteogenesis (DO) is a unique technique for promoting bone formation in clinical practice. However the underlying mechanism remains elusive. As epigenetic mediators, microRNAs have been reported to play important roles in regulating osteogenesis. In this study, after successfully established the DO model of rats, a microRNA microarray was performed to find molecular targets for DO. Total 100 microRNAs were identified as differently expressed, with miR-503 being one of the most significantly up-regulated miRNAs in DO. The further investigation also showed that miR-503 was upregulated during osteogenesis in mesenchymal stem cells of rats, and overexpression of miR-503 significantly promoted osteogenesis in vitro and accelerated mineralization in DO process in vivo. By using bioinformatic investigations and luciferase activities, we successfully demonstrated that Smurf1, a negative regulator of osteogenesis, was a real target of miR-503. Furthermore, Smurf1 knockdown promoted osteogenesis and antagomir-503 abolished the promotive effect, suggesting that miR-503 mediated osteogenic differentiation via suppressing Smurf1 expression. To sum up, these findings indicated that miR-503 promoted osteogenesis and accelerated bone formation, which may shed light on the development for a potential therapeutic target for bone repair.Yuxin SunJia XuLiangliang XuJinfang ZhangKaiming ChanXiaohua PanGang LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yuxin Sun
Jia Xu
Liangliang Xu
Jinfang Zhang
Kaiming Chan
Xiaohua Pan
Gang Li
MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression
description Abstract Distraction osteogenesis (DO) is a unique technique for promoting bone formation in clinical practice. However the underlying mechanism remains elusive. As epigenetic mediators, microRNAs have been reported to play important roles in regulating osteogenesis. In this study, after successfully established the DO model of rats, a microRNA microarray was performed to find molecular targets for DO. Total 100 microRNAs were identified as differently expressed, with miR-503 being one of the most significantly up-regulated miRNAs in DO. The further investigation also showed that miR-503 was upregulated during osteogenesis in mesenchymal stem cells of rats, and overexpression of miR-503 significantly promoted osteogenesis in vitro and accelerated mineralization in DO process in vivo. By using bioinformatic investigations and luciferase activities, we successfully demonstrated that Smurf1, a negative regulator of osteogenesis, was a real target of miR-503. Furthermore, Smurf1 knockdown promoted osteogenesis and antagomir-503 abolished the promotive effect, suggesting that miR-503 mediated osteogenic differentiation via suppressing Smurf1 expression. To sum up, these findings indicated that miR-503 promoted osteogenesis and accelerated bone formation, which may shed light on the development for a potential therapeutic target for bone repair.
format article
author Yuxin Sun
Jia Xu
Liangliang Xu
Jinfang Zhang
Kaiming Chan
Xiaohua Pan
Gang Li
author_facet Yuxin Sun
Jia Xu
Liangliang Xu
Jinfang Zhang
Kaiming Chan
Xiaohua Pan
Gang Li
author_sort Yuxin Sun
title MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression
title_short MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression
title_full MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression
title_fullStr MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression
title_full_unstemmed MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression
title_sort mir-503 promotes bone formation in distraction osteogenesis through suppressing smurf1 expression
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/043522b641d740558735693d5fad70a1
work_keys_str_mv AT yuxinsun mir503promotesboneformationindistractionosteogenesisthroughsuppressingsmurf1expression
AT jiaxu mir503promotesboneformationindistractionosteogenesisthroughsuppressingsmurf1expression
AT liangliangxu mir503promotesboneformationindistractionosteogenesisthroughsuppressingsmurf1expression
AT jinfangzhang mir503promotesboneformationindistractionosteogenesisthroughsuppressingsmurf1expression
AT kaimingchan mir503promotesboneformationindistractionosteogenesisthroughsuppressingsmurf1expression
AT xiaohuapan mir503promotesboneformationindistractionosteogenesisthroughsuppressingsmurf1expression
AT gangli mir503promotesboneformationindistractionosteogenesisthroughsuppressingsmurf1expression
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