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罗汉果甜苷V通过改变微小RNA谱促进糖尿病小鼠骨髓间充质干细胞的成骨分化。

Mogroside V Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells from Diabetic Mice by Altering MicroRNA Profiles.

作者信息

Luo Yicai, Ye Zhimao, Li Cuiping, Hong Le, Li Hao

机构信息

Department of Prosthodontics, College and Affiliated Hospital of Stomatology, Guangxi Medical University, Nanning, 530021, China.

Guangxi Key Laboratory of Oral and Maxillofacial Restoration and Reconstruction, Guangxi Medical University, Nanning, 530021, China.

出版信息

Comb Chem High Throughput Screen. 2025;28(6):998-1010. doi: 10.2174/0113862073299904240416114653.

Abstract

BACKGROUND

Mogroside V (MV), a triterpene glycoside, exhibits diverse biological functions. However, its ability to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under diabetic conditions is yet to be elucidated.

OBJECTIVE

To study the regulation of osteogenic differentiation of BMSCs in diabetic mice by MV and determine the potential mechanism.

METHODS

BMSCs were isolated from both normal (referred to as N-BMSCs) and diabetic (referred to as DM-BMSCs) C57BL/6 mice. DM-BMSCs were treated with different concentrations of MV for varying durations, and cell viability was detected using the cell counting kit-8 assay. Following 2 weeks of osteogenic induction, osteogenic differentiation capability was evaluated using alizarin red S staining, alkaline phosphatase (ALP) activity analysis, and quantitative real-time reverse transcription polymerase chain reaction. Furthermore, the microRNA (miRNA) expression profiles of N-BMSCs, DM-BMSCs, and DM-BMSCs treated with MV were tested using high-throughput sequencing.

RESULTS

Treatment with MV enhanced the viability of DM-BMSCs and mitigated the reduction of calcium nodule deposition, ALP activity, and mRNA expression of ALP, osteocalcin, and runt-related transcription factor 2. Of the analyzed miRNAs, miR-10b-5p was the only one that exhibited differential expression in N-BMSCs, DM-BMSCs, and DM-BMSCs treated with MV. An analysis of the top four protein clusters based on KEGG suggested that the target genes of differentially expressed miRNAs were closely linked to the PI3K/AKT pathway.

CONCLUSION

MV significantly enhances the viability and osteogenic differentiation of BMSCs under diabetic conditions. The alteration of miRNA profiles provides a foundation for further research into the regulatory role of miRNAs and MV in this process.

摘要

背景

罗汉果甜苷V(MV)是一种三萜糖苷,具有多种生物学功能。然而,其在糖尿病条件下促进骨髓间充质干细胞(BMSCs)成骨分化的能力尚未阐明。

目的

研究MV对糖尿病小鼠BMSCs成骨分化的调控作用并确定其潜在机制。

方法

从正常(称为N-BMSCs)和糖尿病(称为DM-BMSCs)C57BL/6小鼠中分离BMSCs。用不同浓度的MV处理DM-BMSCs不同时间,使用细胞计数试剂盒-8检测细胞活力。成骨诱导2周后,通过茜素红S染色、碱性磷酸酶(ALP)活性分析和定量实时逆转录聚合酶链反应评估成骨分化能力。此外,使用高通量测序检测N-BMSCs、DM-BMSCs和经MV处理的DM-BMSCs的微小RNA(miRNA)表达谱。

结果

MV处理可提高DM-BMSCs的活力,并减轻钙结节沉积、ALP活性以及ALP、骨钙素和 runt相关转录因子2 mRNA表达的降低。在所分析的miRNA中,miR-10b-5p是唯一在N-BMSCs、DM-BMSCs和经MV处理的DM-BMSCs中表现出差异表达的miRNA。基于KEGG对前四个蛋白质簇的分析表明,差异表达miRNA的靶基因与PI3K/AKT通路密切相关。

结论

MV可显著提高糖尿病条件下BMSCs的活力和成骨分化能力。miRNA谱的改变为进一步研究miRNA和MV在此过程中的调控作用提供了基础。

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