Ziwei Luo, Jinqi Xie, Haoxiang Ye, Jie Zhang, Yangping Liu, Chunmei Ma, Jiahui Cao, Hao Pan, Xiaosheng Liu, Xianxi Zhou, Jiechen Kong, Dongfeng Chen, Aijun Liu
{"title":"Novel-miR-81 Promotes the Chondrocytes Differentiation of Bone Marrow Mesenchymal Stem Cells Through Inhibiting Rac2 Expression.","authors":"Ziwei Luo, Jinqi Xie, Haoxiang Ye, Jie Zhang, Yangping Liu, Chunmei Ma, Jiahui Cao, Hao Pan, Xiaosheng Liu, Xianxi Zhou, Jiechen Kong, Dongfeng Chen, Aijun Liu","doi":"10.1177/19476035231207778","DOIUrl":null,"url":null,"abstract":"<p><p>ObjectiveMicroRNAs (miRNAs) play a key role in the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Our previous study found that novel-miR-81 can relieve osteoarthritis, but its role in chondrogenic differentiation of BMSCs remains unclear. The purpose of this study was to explore the role of novel-miR-81 in chondrogenic differentiation of BMSCs.MethodsWe used a model in which transforming growth factor (TGF)-β3-induced BMSCs differentiation into chondrocytes. We detected the expression Sox9, Collagen Ⅱ, Aggrecan, novel-miR-81, and Rac2 by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blot was performed to detect the expression of Sox9, Collagen Ⅱ, and Rac2. Dual-luciferase reporter gene assay confirmed that the association between novel-miR-81 and Rac2. In addition, the ectopic chondrocyte differentiation of BMSCs was performed subcutaneously in nude mice. The effect of novel-miR-81 and Rac2 on ectopic chondrogenic differentiation of BMSCs was determined by immunohistochemical staining.ResultsNovel-miR-81 upregulated in chondrogenic differentiation of BMSCs. Rac2 was a key target of novel-miR-81. Mimic novel-miR-81 and siRac2 upregulated the expression of Sox9, Collagen Ⅱ, and Aggrecan.ConclusionNovel-miR-81 promotes the chondrocytes differentiation of BMSCs by inhibiting the expression of target gene Rac2, which provides potential targets for BMSCs transplantation to repair cartilage defects.</p>","PeriodicalId":9626,"journal":{"name":"CARTILAGE","volume":" ","pages":"333-344"},"PeriodicalIF":2.7000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276425/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CARTILAGE","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/19476035231207778","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/24 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ORTHOPEDICS","Score":null,"Total":0}
引用次数: 0
Abstract
ObjectiveMicroRNAs (miRNAs) play a key role in the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Our previous study found that novel-miR-81 can relieve osteoarthritis, but its role in chondrogenic differentiation of BMSCs remains unclear. The purpose of this study was to explore the role of novel-miR-81 in chondrogenic differentiation of BMSCs.MethodsWe used a model in which transforming growth factor (TGF)-β3-induced BMSCs differentiation into chondrocytes. We detected the expression Sox9, Collagen Ⅱ, Aggrecan, novel-miR-81, and Rac2 by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blot was performed to detect the expression of Sox9, Collagen Ⅱ, and Rac2. Dual-luciferase reporter gene assay confirmed that the association between novel-miR-81 and Rac2. In addition, the ectopic chondrocyte differentiation of BMSCs was performed subcutaneously in nude mice. The effect of novel-miR-81 and Rac2 on ectopic chondrogenic differentiation of BMSCs was determined by immunohistochemical staining.ResultsNovel-miR-81 upregulated in chondrogenic differentiation of BMSCs. Rac2 was a key target of novel-miR-81. Mimic novel-miR-81 and siRac2 upregulated the expression of Sox9, Collagen Ⅱ, and Aggrecan.ConclusionNovel-miR-81 promotes the chondrocytes differentiation of BMSCs by inhibiting the expression of target gene Rac2, which provides potential targets for BMSCs transplantation to repair cartilage defects.
目的:MicroRNAs (miRNAs)在骨髓间充质干细胞(BMSCs)向软骨细胞分化过程中发挥关键作用。我们之前的研究发现,novel-miR-81可以缓解骨关节炎,但其在骨髓间充质干细胞软骨分化中的作用尚不清楚。本研究的目的是探讨novel-miR-81在骨髓间充质干细胞成软骨分化中的作用。方法:采用转化生长因子(TGF)-β3诱导BMSCs向软骨细胞分化模型。我们通过实时逆转录-定量聚合酶链反应(RT-qPCR)检测Sox9、CollagenⅡ、Aggrecan、novel-miR-81和Rac2的表达。Western blot检测Sox9、CollagenⅡ、Rac2的表达。双荧光素酶报告基因检测证实了novel-miR-81与Rac2之间的关联。此外,裸鼠皮下进行骨髓间充质干细胞异位软骨细胞分化。通过免疫组织化学染色检测novel-miR-81和Rac2对骨髓间充质干细胞异位软骨分化的影响。结果:novell - mir -81在骨髓间充质干细胞的软骨分化中上调。Rac2是novel-miR-81的关键靶点。Mimic - mir -81和siRac2上调Sox9、CollagenⅡ和Aggrecan的表达。结论:Novel-miR-81通过抑制靶基因Rac2的表达促进骨髓间充质干细胞的软骨细胞分化,为骨髓间充质干细胞移植修复软骨缺损提供了潜在靶点。
期刊介绍:
CARTILAGE publishes articles related to the musculoskeletal system with particular attention to cartilage repair, development, function, degeneration, transplantation, and rehabilitation. The journal is a forum for the exchange of ideas for the many types of researchers and clinicians involved in cartilage biology and repair. A primary objective of CARTILAGE is to foster the cross-fertilization of the findings between clinical and basic sciences throughout the various disciplines involved in cartilage repair.
The journal publishes full length original manuscripts on all types of cartilage including articular, nasal, auricular, tracheal/bronchial, and intervertebral disc fibrocartilage. Manuscripts on clinical and laboratory research are welcome. Review articles, editorials, and letters are also encouraged. The ICRS envisages CARTILAGE as a forum for the exchange of knowledge among clinicians, scientists, patients, and researchers.
The International Cartilage Repair Society (ICRS) is dedicated to promotion, encouragement, and distribution of fundamental and applied research of cartilage in order to permit a better knowledge of function and dysfunction of articular cartilage and its repair.