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木犀草素和芹菜素对体外培养的牙髓细胞中Oct-4、Sox2和c-Myc表达的影响。

Effect of luteolin and apigenin on the expression of Oct-4, Sox2, and c-Myc in dental pulp cells with in vitro culture.

作者信息

Liu Lu, Peng Zhengjun, Xu Zezhen, Wei Xi

机构信息

Operative Dentistry and Endodontics, Guanghua School of Stomatology, Affiliated Stomatological Hospital, Guangdong Province Key Laboratory of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong 510055, China.

出版信息

Biomed Res Int. 2015;2015:534952. doi: 10.1155/2015/534952. Epub 2015 Feb 26.

Abstract

INTRODUCTION

Dental pulp cells (DPCs) are promising cell source for dental tissue regeneration. Recently, small molecules which optimize microenvironment or activate the reprogramming network provide a new way to enhance the pluripotency. Two promising bioflavonoids luteolin and apigenin were reported to enhance reprogramming efficiency in mouse embryonic fibroblast (MEF). However, their effect and underlying mechanism in cell fate determination of human DPCs remain unclear.

METHODS

To elucidate the effect of luteolin and apigenin on the cell fate determination of DPCs, we explored the cell proliferation, cell cycle, senescence, apoptosis, expression of pluripotency markers Oct-4, Sox2, and c-Myc, and multilineage differentiation capability of DPCs with luteolin or apigenin treatment.

RESULTS

We demonstrated that luteolin and apigenin inhibited cell proliferation, arrested DPCs in G2/M and S phase, and upregulated PI value and apoptosis. Moreover, luteolin and apigenin increased telomerase activity, maintained DPCs in a presenescent state, and activated the expression of Oct-4, Sox2, and c-Myc at a dose- and time-dependent pattern in DPCs even at late passages, albeit repressed lineage-specific differentiation.

CONCLUSIONS

Addition of luteolin and apigenin in the culture medium might provide an effective way to maintain DPCs in an undifferentiated stage and inhibit lineage-specific differentiation.

摘要

引言

牙髓细胞(DPCs)是用于牙组织再生的有前景的细胞来源。近来,优化微环境或激活重编程网络的小分子为增强多能性提供了一种新方法。据报道,两种有前景的生物类黄酮木犀草素和芹菜素可提高小鼠胚胎成纤维细胞(MEF)的重编程效率。然而,它们在人牙髓细胞命运决定中的作用及潜在机制仍不清楚。

方法

为阐明木犀草素和芹菜素对牙髓细胞命运决定的影响,我们研究了经木犀草素或芹菜素处理后牙髓细胞的增殖、细胞周期、衰老、凋亡、多能性标志物Oct-4、Sox2和c-Myc的表达以及多谱系分化能力。

结果

我们证明木犀草素和芹菜素抑制细胞增殖,使牙髓细胞停滞于G2/M期和S期,上调PI值并诱导凋亡。此外,木犀草素和芹菜素增加端粒酶活性,使牙髓细胞维持在衰老前状态,并以剂量和时间依赖性方式激活牙髓细胞中Oct-4、Sox2和c-Myc的表达,即使在传代后期也是如此,尽管其抑制了谱系特异性分化。

结论

在培养基中添加木犀草素和芹菜素可能为将牙髓细胞维持在未分化阶段并抑制谱系特异性分化提供一种有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcb/4357035/437181c6fb2d/BMRI2015-534952.001.jpg

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