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Chaetocin通过调节间充质干细胞中的Wnt/β-连环蛋白信号通路促进成骨分化。

Chaetocin Promotes Osteogenic Differentiation via Modulating Wnt/Beta-Catenin Signaling in Mesenchymal Stem Cells.

作者信息

Liang Youde, Liu Xin, Zhou Ruiping, Song Dawei, Jiang Yi-Zhou, Xue Weiwei

机构信息

Department of Stomatology, The Seventh People's Hospital of Shenzhen, China.

Institute for Advanced Study, Shenzhen University, Shenzhen, China.

出版信息

Stem Cells Int. 2021 Feb 6;2021:8888416. doi: 10.1155/2021/8888416. eCollection 2021.

Abstract

Mesenchymal stemXin cells (MSCs) are a great cell source for bone regeneration. Although combining MSCs with growth factors and scaffolds provides a useful clinical strategy for bone tissue engineering, the efficiency of MSC osteogenic differentiation remains to be improved. Epigenetic modification is related to the differentiation ability of MSCs during osteogenic induction. In this study, we evaluate the effect of Chaetocin, an inhibitor of lysine-specific histone methyltransferases, on the differentiation of MSCs. We found that MSCs treated with Chaetocin demonstrated increased osteogenic ability and reduced adipogenic ability. The expression of osteogenic markers (Runx2 and OPN) was induced in MSCs by Chaetocin during osteogenic induction. Moveover, treatment of Chaetocin in MSCs improves Wnt/-catenin signaling pathways and its downstream targets. Finally, we showed increased bone formation of MSC and Wnt/-catenin signaling activity by treatment of Chaetocin using in vivo bone formation assays. Our data uncovered a critical role of Chaetocin in MSC osteogenic differentiation and provide new insights into bone tissue regeneration and repair.

摘要

间充质干细胞(MSCs)是骨再生的优质细胞来源。尽管将间充质干细胞与生长因子和支架相结合为骨组织工程提供了一种有用的临床策略,但间充质干细胞成骨分化的效率仍有待提高。表观遗传修饰与成骨诱导过程中间充质干细胞的分化能力有关。在本研究中,我们评估了赖氨酸特异性组蛋白甲基转移酶抑制剂Chaetocin对间充质干细胞分化的影响。我们发现,用Chaetocin处理的间充质干细胞表现出增强的成骨能力和降低的成脂能力。在成骨诱导过程中,Chaetocin诱导间充质干细胞中成骨标志物(Runx2和OPN)的表达。此外,在间充质干细胞中使用Chaetocin处理可改善Wnt/β-连环蛋白信号通路及其下游靶点。最后,我们通过体内骨形成试验表明,使用Chaetocin处理可增加间充质干细胞的骨形成和Wnt/β-连环蛋白信号活性。我们的数据揭示了Chaetocin在间充质干细胞成骨分化中的关键作用,并为骨组织再生和修复提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3995/7886529/1d5af1ba39bf/SCI2021-8888416.001.jpg

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