Xu Ke, Xiao Jingwen, Zheng Ke, Feng Xingmei, Zhang Jinlong, Song Donghui, Wang Chenfei, Shen Xiang, Zhao Xin, Wei Changbo, Huang Dan, Feng Guijuan
1 Department of Stomatology, Affiliated Hospital of Nantong University , Nantong, China .
2 Department of Stomatology, Wuxi No.2 People's Hospital , Wuxi, China .
Cell Reprogram. 2018 Apr;20(2):107-116. doi: 10.1089/cell.2017.0042. Epub 2018 Mar 16.
Dental pulp stem cells (DPSCs), as one type of mesenchymal stem cells (MSCs), have the capability of self-renewal and multipotency to differentiate into several cell lineages, including osteogenesis, odontoblasts, chondrogenesis, neurogenesis, and adipogenesis. It has found that tumor necrosis factor-α (TNF-α) can promote osteogenic differentiation of human DPSCs in our previous studies. Other experimentation revealed that signal transducer and activator of transcription 3 (STAT3) underwent a rapid activation both in osteogenesis and inflammation microenvironment of MSCs in vitro. MicroRNAs (miRNAs or miRs) have been proved in previous studies to regulate MSCs differentiation in vitro. In this study, we identified miR-21 as a key miRNA contributed the functional axis of odontoblast differentiation induced by STAT3. It is observed that the expression of miR-21 and STAT3 increased gradually in low concentration (1-10 ng/mL) of TNF-α, while they were suppressed in high concentration (50-100 ng/mL). The upregulation of miR-21 may facilitate the odontoblast differentiation of DPSCs coordinating with STAT3. SiSTAT3 or treated by the inhibitor of STAT3, cucurbitacin I (Cuc I), significantly increased primary miR-21 expression along with decreased mature miR-21 expression. Meanwhile, the inhibition of miR-21 (anti-miR-21) decreased the activation of STAT3 as well as suppressed the marker proteins of odontoblast differentiation. The results revealed a new function of miR-21, suggesting that miR-21/STAT3 signal may act as a modulator within a complex network of factors to regulate odontoblast differentiation of human DPSCs. It may provide a novel therapeutic strategy to regulate the odontoblast differentiation of DPSCs.
牙髓干细胞（DPSCs）作为间充质干细胞（MSCs）的一种类型，具有自我更新能力和多能性，能够分化为多种细胞谱系，包括成骨、成牙本质细胞、软骨形成、神经发生和脂肪生成。在我们之前的研究中发现，肿瘤坏死因子-α（TNF-α）可以促进人牙髓干细胞的成骨分化。其他实验表明，信号转导和转录激活因子3（STAT3）在体外MSCs的成骨和炎症微环境中均经历快速激活。在先前的研究中已证明微小RNA（miRNA或miR）可在体外调节MSCs的分化。在本研究中，我们鉴定出miR-21是参与由STAT3诱导的成牙本质细胞分化功能轴的关键miRNA。观察到在低浓度（1-10 ng/mL）的TNF-α中，miR-21和STAT3的表达逐渐增加，而在高浓度（50-100 ng/mL）时它们受到抑制。miR-21的上调可能与STAT3协同促进牙髓干细胞的成牙本质细胞分化。沉默STAT3或用STAT3抑制剂葫芦素I（Cuc I）处理，可显著增加初级miR-21的表达，同时降低成熟miR-21的表达。同时，抑制miR-21（抗miR-21）可降低STAT3的激活，并抑制成牙本质细胞分化的标记蛋白。结果揭示了miR-21的新功能，表明miR-21/STAT3信号可能在复杂的因子网络中作为调节剂来调节人牙髓干细胞的成牙本质细胞分化。它可能为调节牙髓干细胞的成牙本质细胞分化提供一种新的治疗策略。
