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miR-589-3p promoted osteogenic differentiation of periodontal ligament stem cells through targeting ATF1

BACKGROUND: An increasing number of studies have shown that dysregulated miR-589-3p is associated with multiple diseases. However, the role of miR-589-3p in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. This study aimed to explore the biological function and...

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Autores principales: Shi, Fangchuan, He, Rui, Zhu, Jiahao, Lu, Ting, Zhong, Liangjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996605/
https://www.ncbi.nlm.nih.gov/pubmed/35399081
http://dx.doi.org/10.1186/s13018-022-03000-z
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author Shi, Fangchuan
He, Rui
Zhu, Jiahao
Lu, Ting
Zhong, Liangjun
author_facet Shi, Fangchuan
He, Rui
Zhu, Jiahao
Lu, Ting
Zhong, Liangjun
author_sort Shi, Fangchuan
collection PubMed
description BACKGROUND: An increasing number of studies have shown that dysregulated miR-589-3p is associated with multiple diseases. However, the role of miR-589-3p in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. This study aimed to explore the biological function and potential molecular mechanism of miR-589-3p in osteogenic differentiation of PDLSCs. METHODS: GSE159508 was downloaded from Gene Expression Omibus (GEO, http://www.ncbi.nlm.nih.gov/geo/). Differentially expressed miRNAs between osteogenic induction PDLSCs versus non-induction PDLSCs were obtained by R software. miR-589-3p mimic and miR-589-3p inhibitor and corresponding negative control were obtained and to identify the role of miR-589-3p in osteogenic differentiation of PDLSCs. ALP staining and ARS were used to evaluate ALP activity and mineralization, respectively. The targeted binding relationship between miR-589-3p and ATF1 was predicted and verified by target prediction analysis and dual-luciferase assay. Furthermore, the functional mechanism based on miR-589-3p and ATF1 in osteogenic differentiation of PDLSCs was further investigated through rescue experiments. RESULTS: According to the cut-off criteria with log 2 FC > 1.0 and P < 0.05, 514 differentially expressed miRNAs were identified between osteogenic induction and non-induction PDLSCs, including 309 upregulated miRNAs and 205 downregulated miRNAs. Compared with control PDLSCs, miR-589-3p expression level was notably increased in PDLSCs that underwent osteogenic induction. The overexpression of miR-589-3p promoted the cell viability of PDLSCs, while the low expression of miR-589-3p had the opposite effect. The dual luciferase reporter assay verified that ATF1 was proved to be a direct target of miR-589-3p in PDLSCs. And overexpressed miR-589-3p reduced the expression of ATF1. Overexpression of miR-589-3p enhanced the osteogenic capacity of PDLSCs, as demonstrated by increases in ALP activity, matrix mineralization, and RUNX2, OCN and OSX expression. In addition, the rescue experiments confirmed that overexpressed ATF1 restored the effects of overexpressed miR-589-3p on cell proliferation and osteogenic differentiation of PDLSCs. CONCLUSION: miR-589-3p could down-regulate the expression of ATF1, thereby promote the proliferation and osteogenic differentiation of PDLSCs. This finding may provide a new therapeutic target for molecular therapy of periodontitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13018-022-03000-z.
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spelling pubmed-89966052022-04-12 miR-589-3p promoted osteogenic differentiation of periodontal ligament stem cells through targeting ATF1 Shi, Fangchuan He, Rui Zhu, Jiahao Lu, Ting Zhong, Liangjun J Orthop Surg Res Research Article BACKGROUND: An increasing number of studies have shown that dysregulated miR-589-3p is associated with multiple diseases. However, the role of miR-589-3p in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remains unknown. This study aimed to explore the biological function and potential molecular mechanism of miR-589-3p in osteogenic differentiation of PDLSCs. METHODS: GSE159508 was downloaded from Gene Expression Omibus (GEO, http://www.ncbi.nlm.nih.gov/geo/). Differentially expressed miRNAs between osteogenic induction PDLSCs versus non-induction PDLSCs were obtained by R software. miR-589-3p mimic and miR-589-3p inhibitor and corresponding negative control were obtained and to identify the role of miR-589-3p in osteogenic differentiation of PDLSCs. ALP staining and ARS were used to evaluate ALP activity and mineralization, respectively. The targeted binding relationship between miR-589-3p and ATF1 was predicted and verified by target prediction analysis and dual-luciferase assay. Furthermore, the functional mechanism based on miR-589-3p and ATF1 in osteogenic differentiation of PDLSCs was further investigated through rescue experiments. RESULTS: According to the cut-off criteria with log 2 FC > 1.0 and P < 0.05, 514 differentially expressed miRNAs were identified between osteogenic induction and non-induction PDLSCs, including 309 upregulated miRNAs and 205 downregulated miRNAs. Compared with control PDLSCs, miR-589-3p expression level was notably increased in PDLSCs that underwent osteogenic induction. The overexpression of miR-589-3p promoted the cell viability of PDLSCs, while the low expression of miR-589-3p had the opposite effect. The dual luciferase reporter assay verified that ATF1 was proved to be a direct target of miR-589-3p in PDLSCs. And overexpressed miR-589-3p reduced the expression of ATF1. Overexpression of miR-589-3p enhanced the osteogenic capacity of PDLSCs, as demonstrated by increases in ALP activity, matrix mineralization, and RUNX2, OCN and OSX expression. In addition, the rescue experiments confirmed that overexpressed ATF1 restored the effects of overexpressed miR-589-3p on cell proliferation and osteogenic differentiation of PDLSCs. CONCLUSION: miR-589-3p could down-regulate the expression of ATF1, thereby promote the proliferation and osteogenic differentiation of PDLSCs. This finding may provide a new therapeutic target for molecular therapy of periodontitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13018-022-03000-z. BioMed Central 2022-04-10 /pmc/articles/PMC8996605/ /pubmed/35399081 http://dx.doi.org/10.1186/s13018-022-03000-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Shi, Fangchuan
He, Rui
Zhu, Jiahao
Lu, Ting
Zhong, Liangjun
miR-589-3p promoted osteogenic differentiation of periodontal ligament stem cells through targeting ATF1
title miR-589-3p promoted osteogenic differentiation of periodontal ligament stem cells through targeting ATF1
title_full miR-589-3p promoted osteogenic differentiation of periodontal ligament stem cells through targeting ATF1
title_fullStr miR-589-3p promoted osteogenic differentiation of periodontal ligament stem cells through targeting ATF1
title_full_unstemmed miR-589-3p promoted osteogenic differentiation of periodontal ligament stem cells through targeting ATF1
title_short miR-589-3p promoted osteogenic differentiation of periodontal ligament stem cells through targeting ATF1
title_sort mir-589-3p promoted osteogenic differentiation of periodontal ligament stem cells through targeting atf1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996605/
https://www.ncbi.nlm.nih.gov/pubmed/35399081
http://dx.doi.org/10.1186/s13018-022-03000-z
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