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BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats

BACKGROUND: In the bone marrow microenvironment of postmenopausal osteoporosis (PMOP), bone marrow mesenchymal stem cell (BMSC)-derived exosomal miRNAs play an important role in bone formation and bone resorption, although the pathogenesis has yet to be clarified. METHODS: BMSC-derived exosomes from...

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Autores principales: Lai, Guohua, Zhao, Renli, Zhuang, Weida, Hou, Zuoxu, Yang, Zefeng, He, Peipei, Wu, Jiachang, Sang, Hongxun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509671/
https://www.ncbi.nlm.nih.gov/pubmed/36168439
http://dx.doi.org/10.7717/peerj.13744
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author Lai, Guohua
Zhao, Renli
Zhuang, Weida
Hou, Zuoxu
Yang, Zefeng
He, Peipei
Wu, Jiachang
Sang, Hongxun
author_facet Lai, Guohua
Zhao, Renli
Zhuang, Weida
Hou, Zuoxu
Yang, Zefeng
He, Peipei
Wu, Jiachang
Sang, Hongxun
author_sort Lai, Guohua
collection PubMed
description BACKGROUND: In the bone marrow microenvironment of postmenopausal osteoporosis (PMOP), bone marrow mesenchymal stem cell (BMSC)-derived exosomal miRNAs play an important role in bone formation and bone resorption, although the pathogenesis has yet to be clarified. METHODS: BMSC-derived exosomes from ovariectomized rats (OVX-Exo) and sham-operated rats (Sham-Exo) were co-cultured with bone marrow-derived macrophages to study their effects on osteoclast differentiation. Next-generation sequencing was utilized to identify the differentially expressed miRNAs (DE-miRNAs) between OVX-Exo and Sham-Exo, while target genes were analyzed using bioinformatics. The regulatory effects of miR-27a-3p and miR-196b-5p on osteogenic differentiation of BMSCs and osteoclast differentiation were verified by gain-of-function and loss-of-function analyses. RESULTS: Osteoclast differentiation was significantly enhanced in the OVX-Exo treatment group compared to the Sham-Exo group. Twenty DE-miRNAs were identified between OVX-Exo and Sham-Exo, among which miR-27a-3p and miR-196b-5p promoted the expressions of osteogenic differentiation markers in BMSCs. In contrast, knockdown of miR-27a-3p and miR-196b-5p increased the expressions of osteoclastic markers in osteoclast. These 20 DE-miRNAs were found to target 11435 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these target genes were involved in several biological processes and osteoporosis-related signaling pathways. CONCLUSION: BMSC-derived exosomal miR-27a-3p and miR-196b-5p may play a positive regulatory role in bone remodeling.
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spelling pubmed-95096712022-09-26 BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats Lai, Guohua Zhao, Renli Zhuang, Weida Hou, Zuoxu Yang, Zefeng He, Peipei Wu, Jiachang Sang, Hongxun PeerJ Bioinformatics BACKGROUND: In the bone marrow microenvironment of postmenopausal osteoporosis (PMOP), bone marrow mesenchymal stem cell (BMSC)-derived exosomal miRNAs play an important role in bone formation and bone resorption, although the pathogenesis has yet to be clarified. METHODS: BMSC-derived exosomes from ovariectomized rats (OVX-Exo) and sham-operated rats (Sham-Exo) were co-cultured with bone marrow-derived macrophages to study their effects on osteoclast differentiation. Next-generation sequencing was utilized to identify the differentially expressed miRNAs (DE-miRNAs) between OVX-Exo and Sham-Exo, while target genes were analyzed using bioinformatics. The regulatory effects of miR-27a-3p and miR-196b-5p on osteogenic differentiation of BMSCs and osteoclast differentiation were verified by gain-of-function and loss-of-function analyses. RESULTS: Osteoclast differentiation was significantly enhanced in the OVX-Exo treatment group compared to the Sham-Exo group. Twenty DE-miRNAs were identified between OVX-Exo and Sham-Exo, among which miR-27a-3p and miR-196b-5p promoted the expressions of osteogenic differentiation markers in BMSCs. In contrast, knockdown of miR-27a-3p and miR-196b-5p increased the expressions of osteoclastic markers in osteoclast. These 20 DE-miRNAs were found to target 11435 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these target genes were involved in several biological processes and osteoporosis-related signaling pathways. CONCLUSION: BMSC-derived exosomal miR-27a-3p and miR-196b-5p may play a positive regulatory role in bone remodeling. PeerJ Inc. 2022-09-22 /pmc/articles/PMC9509671/ /pubmed/36168439 http://dx.doi.org/10.7717/peerj.13744 Text en ©2022 Lai et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Bioinformatics
Lai, Guohua
Zhao, Renli
Zhuang, Weida
Hou, Zuoxu
Yang, Zefeng
He, Peipei
Wu, Jiachang
Sang, Hongxun
BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats
title BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats
title_full BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats
title_fullStr BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats
title_full_unstemmed BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats
title_short BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats
title_sort bmsc-derived exosomal mir-27a-3p and mir-196b-5p regulate bone remodeling in ovariectomized rats
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509671/
https://www.ncbi.nlm.nih.gov/pubmed/36168439
http://dx.doi.org/10.7717/peerj.13744
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