通过转录组分析鉴定参与胶原水凝胶诱导间充质干细胞软骨分化的关键基因:m6A修饰的作用。

IF 4.2 3区 医学 Q2 ENGINEERING, BIOMEDICAL Journal of Materials Science: Materials in Medicine Pub Date : 2024-07-29 DOI:10.1007/s10856-024-06801-2
Chaotao Chen, Kai Xiong, Kanglu Li, Bo Zhou, Jianwen Cheng, Bo Zhu, Li Zheng, Jinmin Zhao
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引用次数: 0

摘要

胶原水凝胶作为骨髓间充质干细胞(BMSCs)软骨分化的诱导剂,有助于软骨缺损的修复。然而,这一现象背后的确切分子机制仍未阐明。在这里,我们使用胶原水凝胶诱导了骨髓造血干细胞的软骨分化,并通过转录组测序鉴定了4451个差异表达基因(DEGs)。我们的分析表明,DEGs富集于局灶粘附通路,与对照组相比,胶原水凝胶组的表达水平明显下降。蛋白-蛋白相互作用网络分析表明,肌动蛋白α1(ACTN1)和肌动蛋白α4(ACTN4)这两种也参与细胞骨架重组的蛋白可能在胶原水凝胶诱导的BMSCs软骨分化中起着关键作用。此外,我们还发现 N6-甲基腺苷 RNA 甲基化(m6A)修饰参与了胶原水凝胶介导的软骨分化,脂肪量和肥胖相关蛋白(FTO)与 ACTN1 和 ACTN4 的表达调控有关。这些发现表明,胶原水凝胶可能通过 FTO 介导的 m6A 修饰下调 ACTN1 和 ACTN4 mRNA,从而调节病灶粘附和肌动蛋白细胞骨架信号通路,最终驱动 BMSCs 的软骨分化。总之,我们的研究为胶原水凝胶诱导 BMSCs 软骨分化的分子机制提供了有价值的见解,有助于开发更有效的软骨再生策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Identification of key genes involved in collagen hydrogel-induced chondrogenic differentiation of mesenchymal stem cells through transcriptome analysis: the role of m6A modification

Collagen hydrogel has been shown promise as an inducer for chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), contributing to the repair of cartilage defects. However, the precise molecular mechanism underlying this phenomenon remains poorly elucidated. Here, we induced chondrogenic differentiation of BMSCs using collagen hydrogel and identified 4451 differentially expressed genes (DEGs) through transcriptomic sequencing. Our analysis revealed that DEGs were enriched in the focal adhesion pathway, with a notable decrease in expression levels in the collagen hydrogel group compared to the control group. Protein-protein interaction network analysis suggested that actinin alpha 1 (ACTN1) and actinin alpha 4 (ACTN4), two proteins also involved in cytoskeletal recombination, may be crucial in collagen hydrogel-induced chondrogenic differentiation of BMSCs. Additionally, we found that N6-methyladenosine RNA methylation (m6A) modification was involved in collagen hydrogel-mediated chondrogenic differentiation, with fat mass and obesity-associated protein (FTO) implicated in regulating the expression of ACTN1 and ACTN4. These findings suggest that collagen hydrogel might regulate focal adhesion and actin cytoskeletal signaling pathways through down-regulation of ACTN1 and ACTN4 mRNA via FTO-mediated m6A modification, ultimately driving chondrogenic differentiation of BMSCs. In conclusion, our study provides valuable insights into the molecular mechanisms of collagen hydrogel-induced chondrogenic differentiation of BMSCs, which may aid in developing more effective strategies for cartilage regeneration.

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来源期刊
Journal of Materials Science: Materials in Medicine
Journal of Materials Science: Materials in Medicine 工程技术-材料科学:生物材料
CiteScore
8.00
自引率
0.00%
发文量
73
审稿时长
3.5 months
期刊介绍: The Journal of Materials Science: Materials in Medicine publishes refereed papers providing significant progress in the application of biomaterials and tissue engineering constructs as medical or dental implants, prostheses and devices. Coverage spans a wide range of topics from basic science to clinical applications, around the theme of materials in medicine and dentistry. The central element is the development of synthetic and natural materials used in orthopaedic, maxillofacial, cardiovascular, neurological, ophthalmic and dental applications. Special biomedical topics include biomaterial synthesis and characterisation, biocompatibility studies, nanomedicine, tissue engineering constructs and cell substrates, regenerative medicine, computer modelling and other advanced experimental methodologies.
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