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人骨髓间充质干细胞在软骨形成过程中的表观遗传调控的初步特征。

Preliminary Characterization of the Epigenetic Modulation in the Human Mesenchymal Stem Cells during Chondrogenic Process.

机构信息

Department of Neuroscience, Reproductive and Odontostomatological Sciences, University of Naples "Federico II", 80131 Naples, Italy.

CEINGE Biotecnologie Avanzate, 80145 Naples, Italy.

出版信息

Int J Mol Sci. 2022 Aug 30;23(17):9870. doi: 10.3390/ijms23179870.

DOI:10.3390/ijms23179870
PMID:36077266
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9456537/
Abstract

Regenerative medicine represents a growing hot topic in biomedical sciences, aiming at setting out novel therapeutic strategies to repair or regenerate damaged tissues and organs. For this perspective, human mesenchymal stem cells (hMSCs) play a key role in tissue regeneration, having the potential to differentiate into many cell types, including chondrocytes. Accordingly, in the last few years, researchers have focused on several in vitro strategies to optimize hMSC differentiation protocols, including those relying on epigenetic manipulations that, in turn, lead to the modulation of gene expression patterns. Therefore, in the present study, we investigated the role of the class II histone deacetylase (HDAC) inhibitor, MC1568, in the hMSCs-derived chondrogenesis. The hMSCs we used for this work were the hMSCs obtained from the amniotic fluid, given their greater differentiation capacity. Our preliminary data documented that MC1568 drove both the improvement and acceleration of hMSCs chondrogenic differentiation in vitro, since the differentiation process in MC1568-treated cells took place in about seven days, much less than that normally observed, namely 21 days. Collectively, these preliminary data might shed light on the validity of such a new differentiative protocol, in order to better assess the potential role of the epigenetic modulation in the process of the hypertrophic cartilage formation, which represents the starting point for endochondral ossification.

摘要

再生医学代表了生物医学科学中一个日益热门的话题,旨在制定新的治疗策略来修复或再生受损的组织和器官。就这方面而言,人类间充质干细胞 (hMSCs) 在组织再生中起着关键作用,具有分化为多种细胞类型的潜力,包括软骨细胞。因此,在过去几年中,研究人员专注于几种体外策略来优化 hMSC 分化方案,包括依赖于表观遗传操作的方案,这些操作反过来又导致基因表达模式的调节。因此,在本研究中,我们研究了 II 类组蛋白去乙酰化酶 (HDAC) 抑制剂 MC1568 在 hMSC 软骨分化中的作用。我们用于这项工作的 hMSCs 是从羊水获得的 hMSCs,因为它们具有更大的分化能力。我们的初步数据记录表明,MC1568 既促进了 hMSCs 的体外软骨分化,又加速了这一过程,因为在 MC1568 处理的细胞中,分化过程发生在大约七天内,比正常观察到的 21 天要短得多。总的来说,这些初步数据可能揭示了这种新的分化方案的有效性,以便更好地评估表观遗传调节在肥大软骨形成过程中的潜在作用,这是软骨内骨化的起点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15ed/9456537/f76f53f8d243/ijms-23-09870-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15ed/9456537/b3330dad8c81/ijms-23-09870-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15ed/9456537/d4a4f1996d42/ijms-23-09870-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15ed/9456537/f76f53f8d243/ijms-23-09870-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15ed/9456537/b3330dad8c81/ijms-23-09870-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15ed/9456537/d4a4f1996d42/ijms-23-09870-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15ed/9456537/f76f53f8d243/ijms-23-09870-g003.jpg

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A knock-in rat model unravels acute and chronic renal toxicity in glutaric aciduria type I.谷氨酸尿症 I 型的急性和慢性肾毒性的基因敲入大鼠模型。
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