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miR-483-3p 通过靶向 ARRB2 促进牙髓干细胞成骨分化通过 MAPK 信号通路。

MiR-483-3p promotes dental pulp stem cells osteogenic differentiation via the MAPK signaling pathway by targeting ARRB2.

机构信息

Department of Orthodontics and Periodontology, Affiliated Nantong Stomatological Hospital of Nantong University, 36 South Yuelong Road, Nantong, 226001, China.

Department of Immunology, School of Medicine, Nantong University, Nantong, China.

出版信息

In Vitro Cell Dev Biol Anim. 2024 Sep;60(8):879-887. doi: 10.1007/s11626-024-00929-9. Epub 2024 Jun 4.

Abstract

Human dental pulp stem cells (DPSCs) have become an important component for bone tissue engineering and regenerative medicine due to their ability to differentiate into osteoblast precursors. Two miRNA chip datasets (GSE138180 and E-MTAB-3077) of DPSCs osteogenic differentiation were analyzed respectively to find the expression of miR-483-3p significantly increased in the differentiated groups. We further confirmed that miR-483-3p continued to overexpress during osteogenic differentiation of DPSCs, especially reaching its peak on the 7th day. Moreover, miR-483-3p could significantly promote the expression of osteogenic markers including RUNX2 and OSX, and activate MAPK signaling pathway by inducing phosphorylation of ERK, p38, and JNK. In addition, as a significant gene within the MAPK signaling pathway, ARRB2 was identified as the target gene of miR-483-3p by bioinformatic prediction and experimental verification. In conclusion, we identified miR-483-3p could promote osteogenic differentiation of DPSCs via the MAPK signaling pathway by targeting ARRB2.

摘要

人牙髓干细胞(DPSCs)由于其能够分化为成骨前体细胞而成为骨组织工程和再生医学的重要组成部分。对 DPSCs 成骨分化的两个 miRNA 芯片数据集(GSE138180 和 E-MTAB-3077)进行了分别分析,发现 miR-483-3p 的表达在分化组中明显增加。我们进一步证实,miR-483-3p 在 DPSCs 的成骨分化过程中持续过表达,特别是在第 7 天达到峰值。此外,miR-483-3p 可以通过诱导 ERK、p38 和 JNK 的磷酸化来显著促进成骨标志物包括 RUNX2 和 OSX 的表达,并激活 MAPK 信号通路。此外,作为 MAPK 信号通路中的一个重要基因,ARRB2 被确定为 miR-483-3p 的靶基因,通过生物信息学预测和实验验证。总之,我们发现 miR-483-3p 可以通过靶向 ARRB2 来促进 DPSCs 的成骨分化。

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