miR-378a-3p 调控 BMP2-Smad 通路,促进滑膜衍生间充质干细胞的软骨分化

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Biochemistry and Biophysics Pub Date : 2024-10-07 DOI:10.1007/s12013-024-01561-w
Xiangyi Sun, Ruchao Long, Qiang Chen, Jian Feng, Yang Gao, Guangqi Zhu, Zhihua Yang
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引用次数: 0

摘要

本研究旨在阐明miR-378a-3p在促进滑膜间充质干细胞(SMSCs)增殖和分化为软骨细胞中的作用。我们通过组织学分析、定量 PCR 和 Western 印迹法研究了过表达 miR-378a-3p 对 SMSCs 的影响。然后,我们通过基因本体论和京都基因和基因组百科全书的分析以及 RegRNA 2.0 数据库的预测,确定了 miR-378a-3p 与 BMP2 的结合位点。随后,利用荧光素酶报告基因实验和miR-378a-3p RNA干扰质粒证实了BMP2是miR-378a-3p促进SMSCs软骨分化的靶点。最后,我们通过构建大鼠关节软骨损伤模型,检测了miR-378a-3p过表达对软骨损伤的修复作用。此外,我们还验证了 miR-378a-3p 促进 SMSCs 软骨分化的机制。MiR-378a-3p通过调节BMP2-Smad信号通路,促进SMSCs增殖和分化为软骨细胞,从而促进大鼠关节软骨损伤的修复过程。值得注意的是,敲除 BMP2 会降低 miR-378a-3p 对关节软骨损伤的修复功效。miR-378a-3p的上调通过激活BMP2-Smad通路促进SMSCs的软骨分化,使其成为骨关节炎的潜在治疗靶点。
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miR-378a-3p Regulates the BMP2-Smad Pathway to Promote Chondrogenic Differentiation of Synovium-Derived Mesenchymal Stem Cells.

This study aims to elucidate the role of miR-378a-3p in facilitating the proliferation and differentiation of synovium-derived mesenchymal stem cells (SMSCs) into chondrocytes. The effects of overexpressing miR-378a-3p on SMSCs were investigated through histological analysis, quantitative PCR, and western blotting. Then we identified binding sites of miR-378a-3p with BMP2 through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses and predictions from the RegRNA 2.0 database. Subsequently, BMP2 was confirmed as the target by which miR-378a-3p promotes the chondrogenic differentiation of SMSCs using a luciferase reporter gene assay and an miR-378a-3p RNA interference plasmid. Finally, by constructing a rat model with articular cartilage damage, we detected the reparative effects of miR-378a-3p overexpression on cartilage damage. Additionally, we verified the mechanism by which miR-378a-3p promotes chondrogenic differentiation in SMSCs. MiR-378a-3p enhances the proliferation and differentiation of SMSCs into chondrocytes by modulating the BMP2-Smad signaling pathway, thereby facilitating repair processes for articular cartilage injuries in rats. Notably, knockdown of BMP2 diminished the reparative efficacy of miR-378a-3p on articular cartilage damage. Upregulation of miR-378a-3p promotes chondrogenic differentiation in SMSCs through activation of the BMP2-Smad pathway, positioning it as a potential therapeutic target for osteoarthritis.

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来源期刊
Cell Biochemistry and Biophysics
Cell Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
72
审稿时长
7.5 months
期刊介绍: Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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