{"title":"miR-34a-5p通过靶向HDAC1，促进ER-α转录，促进骨髓间充质干细胞成骨分化，调节骨代谢。","authors":"Dawei Sun, Yuhui Chen, Xiaochun Liu, Guoying Huang, Guoyun Cheng, Chaoqun Yu, Jia Fang","doi":"10.1080/03008207.2022.2108415","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Metabolism is essential for bone development. The expressions of catabolic markers in chondrocytes show association with miR-34a-5p. This study discussed the mechanism by which miR-34a-5p regulates osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) as well as bone metabolism.</p><p><strong>Methods: </strong>Expressions of BMSC surface markers were determined via flow cytometry. Osteogenic differentiation of BMSCs was subsequently induced. miR-34a-5p mimic, oe-HDAC1, or ER-α activator Ferutinin was introduced in BMSCs. Alkaline phosphatase activity and calcification were detected. Expressions of miR-34a-5p, HDAC1, ER-α, and osteogenic markers were determined via RT-qPCR and Western blot. The binding relationship between miR-34a-5p and HDAC1 was verified by a dual-luciferase assay. Mice at the age of 6 months and 18 months were assigned to the young group and age group for in vivo experiments, and aged mice were treated with agomiR miR-34a-5p. Expressions of serum miR-34a-5p, HDAC1, ER-α, and bone metabolism markers in mice were determined.</p><p><strong>Results: </strong>Osteogenic medium-induced BMSCs manifested increased expressions of miR-34a-5p and ER-α and decreased HDAC1 expression. miR-34a-5p overexpression promoted osteogenic differentiation of BMSCs. miR-34a-5p targeted HDAC1. HDAC1 overexpression partially counteracted the promotional action of miR-34a-5p overexpression on osteogenic differentiation of BMSCs. miR-34a-5p overexpression activated ER-α. ER-α activator Ferutinin partially nullified the regulatory function of miR-34a-5p/HDAC1 on osteogenic differentiation of BMSCs. In vivo experiments showed that miR-34a-5p overexpression enhanced the potential of bone metabolism in aged mice.</p><p><strong>Conclusion: </strong>miR-34a-5p overexpression promoted osteogenic differentiation of BMSCs and enhanced bone metabolism by promoting ER-α activation via targeting HDAC1.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"64 2","pages":"126-138"},"PeriodicalIF":2.8000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"miR-34a-5p facilitates osteogenic differentiation of bone marrow mesenchymal stem cells and modulates bone metabolism by targeting HDAC1 and promoting ER-α transcription.\",\"authors\":\"Dawei Sun, Yuhui Chen, Xiaochun Liu, Guoying Huang, Guoyun Cheng, Chaoqun Yu, Jia Fang\",\"doi\":\"10.1080/03008207.2022.2108415\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Metabolism is essential for bone development. The expressions of catabolic markers in chondrocytes show association with miR-34a-5p. This study discussed the mechanism by which miR-34a-5p regulates osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) as well as bone metabolism.</p><p><strong>Methods: </strong>Expressions of BMSC surface markers were determined via flow cytometry. Osteogenic differentiation of BMSCs was subsequently induced. miR-34a-5p mimic, oe-HDAC1, or ER-α activator Ferutinin was introduced in BMSCs. Alkaline phosphatase activity and calcification were detected. Expressions of miR-34a-5p, HDAC1, ER-α, and osteogenic markers were determined via RT-qPCR and Western blot. The binding relationship between miR-34a-5p and HDAC1 was verified by a dual-luciferase assay. Mice at the age of 6 months and 18 months were assigned to the young group and age group for in vivo experiments, and aged mice were treated with agomiR miR-34a-5p. Expressions of serum miR-34a-5p, HDAC1, ER-α, and bone metabolism markers in mice were determined.</p><p><strong>Results: </strong>Osteogenic medium-induced BMSCs manifested increased expressions of miR-34a-5p and ER-α and decreased HDAC1 expression. miR-34a-5p overexpression promoted osteogenic differentiation of BMSCs. miR-34a-5p targeted HDAC1. HDAC1 overexpression partially counteracted the promotional action of miR-34a-5p overexpression on osteogenic differentiation of BMSCs. miR-34a-5p overexpression activated ER-α. ER-α activator Ferutinin partially nullified the regulatory function of miR-34a-5p/HDAC1 on osteogenic differentiation of BMSCs. In vivo experiments showed that miR-34a-5p overexpression enhanced the potential of bone metabolism in aged mice.</p><p><strong>Conclusion: </strong>miR-34a-5p overexpression promoted osteogenic differentiation of BMSCs and enhanced bone metabolism by promoting ER-α activation via targeting HDAC1.</p>\",\"PeriodicalId\":10661,\"journal\":{\"name\":\"Connective Tissue Research\",\"volume\":\"64 2\",\"pages\":\"126-138\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Connective Tissue Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/03008207.2022.2108415\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Connective Tissue Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/03008207.2022.2108415","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
miR-34a-5p facilitates osteogenic differentiation of bone marrow mesenchymal stem cells and modulates bone metabolism by targeting HDAC1 and promoting ER-α transcription.
Objective: Metabolism is essential for bone development. The expressions of catabolic markers in chondrocytes show association with miR-34a-5p. This study discussed the mechanism by which miR-34a-5p regulates osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) as well as bone metabolism.
Methods: Expressions of BMSC surface markers were determined via flow cytometry. Osteogenic differentiation of BMSCs was subsequently induced. miR-34a-5p mimic, oe-HDAC1, or ER-α activator Ferutinin was introduced in BMSCs. Alkaline phosphatase activity and calcification were detected. Expressions of miR-34a-5p, HDAC1, ER-α, and osteogenic markers were determined via RT-qPCR and Western blot. The binding relationship between miR-34a-5p and HDAC1 was verified by a dual-luciferase assay. Mice at the age of 6 months and 18 months were assigned to the young group and age group for in vivo experiments, and aged mice were treated with agomiR miR-34a-5p. Expressions of serum miR-34a-5p, HDAC1, ER-α, and bone metabolism markers in mice were determined.
Results: Osteogenic medium-induced BMSCs manifested increased expressions of miR-34a-5p and ER-α and decreased HDAC1 expression. miR-34a-5p overexpression promoted osteogenic differentiation of BMSCs. miR-34a-5p targeted HDAC1. HDAC1 overexpression partially counteracted the promotional action of miR-34a-5p overexpression on osteogenic differentiation of BMSCs. miR-34a-5p overexpression activated ER-α. ER-α activator Ferutinin partially nullified the regulatory function of miR-34a-5p/HDAC1 on osteogenic differentiation of BMSCs. In vivo experiments showed that miR-34a-5p overexpression enhanced the potential of bone metabolism in aged mice.
Conclusion: miR-34a-5p overexpression promoted osteogenic differentiation of BMSCs and enhanced bone metabolism by promoting ER-α activation via targeting HDAC1.
期刊介绍：
The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology.
The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented.
The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including
Biochemistry
Cell and Molecular Biology
Immunology
Structural Biology
Biophysics
Biomechanics
Regenerative Medicine
The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.
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