Hsa-let-7c controls the committed differentiation of IGF-1-treated mesenchymal stem cells derived from dental pulps by targeting IGF-1R via the MAPK pathways.
Hsa-let-7c controls the committed differentiation of IGF-1-treated mesenchymal stem cells derived from dental pulps by targeting IGF-1R via the MAPK pathways.
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DOI：
10.1038/s12276-018-0048-7
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发表时间：
2018-04-13
影响因子：
12.8
通讯作者：
Yu JH
中科院分区：
文献类型：
--
作者：
Liu GX;Ma S;Li Y;Yu Y;Zhou YX;Lu YD;Jin L;Wang ZL;Yu JH
假定的肿瘤抑制因子 microRNA let-7c 与癌细胞的生物学特性广泛相关。然而，let-7c 在间充质干细胞分化中的潜在参与尚未得到充分探索。在本研究中，我们通过流式细胞术、CCK-8 检测、茜素红染色、实时 RT-PCR 和蛋白质印迹研究了 hsa-let-7c (let-7c) 对胰岛素样生长因子 1 (IGF-1) 处理的人牙髓源性间充质干细胞 (DPMSC) 增殖和分化的影响。一般来说，let-7c的过表达或缺失不会显着影响DPMSCs的增殖能力和细胞活力。然而，let-7c 的过表达显着抑制 IGF-1 受体 (IGF-1R) 的表达，并下调 DPMSC 的骨/牙源性分化，如 IGF-1 处理中几种骨/牙源性标记物（骨钙素、osterix、runt 相关转录因子 2、牙本质唾液酸磷蛋白、牙本质唾液蛋白、碱性磷酸酶、1 型胶原和牙本质基质蛋白 1）水平降低所表明的。 DPMSC。相反，let-7c 的缺失导致 IGF-1R 水平增加并增强骨/牙源性分化。此外，在DPMSCs中过度表达let-7c后，ERK、JNK和P38 MAPK通路受到显着抑制。 let-7c 的缺失促进了 JNK 和 P38 MAPK 通路的激活。我们的累积研究结果表明，Let-7c 可以通过 JNK/P38 MAPK 信号通路靶向 IGF-1R，从而抑制 IGF-1 处理的 DPMSC 的骨/牙源性分化。一种小的非编码 RNA 分子可以通过中断生长因子信号来控制干细胞向骨细胞的转化。胰岛素样生长因子 1 (IGF-1) 是骨骼中最丰富的生长因子，已知可以触发干细胞转化为骨细胞。 microRNA let-7c 主要被称为肿瘤抑制因子，也被认为参与骨生成。然而，人们对这两个分子之间的相互作用知之甚少。中国南京医科大学的 Jinhua Yu 和同事用 let-7c 处理从牙髓收集的干细胞，然后评估它们的矿化，这表明骨的形成。他们发现增加 let-7c 浓度可以通过阻断 IGF-1 信号来抑制向骨的转化。删除let-7c 会产生相反的效果。这些发现可能有助于牙齿工程和骨骼重建的进一步研究。
The putative tumor suppressor microRNA let-7c is extensively associated with the biological properties of cancer cells. However, the potential involvement of let-7c in the differentiation of mesenchymal stem cells has not been fully explored. In this study, we investigated the influence of hsa-let-7c (let-7c) on the proliferation and differentiation of human dental pulp-derived mesenchymal stem cells (DPMSCs) treated with insulin-like growth factor 1 (IGF-1) via flow cytometry, CCK-8 assays, alizarin red staining, real-time RT-PCR, and western blotting. In general, the proliferative capabilities and cell viability of DPMSCs were not significantly affected by the overexpression or deletion of let-7c. However, overexpression of let-7c significantly inhibited the expression of IGF-1 receptor (IGF-1R) and downregulated the osteo/odontogenic differentiation of DPMSCs, as indicated by decreased levels of several osteo/odontogenic markers (osteocalcin, osterix, runt-related transcription factor 2, dentin sialophosphoprotein, dentin sialoprotein, alkaline phosphatase, type 1 collagen, and dentin matrix protein 1) in IGF-1-treated DPMSCs. Inversely, deletion of let-7c resulted in increased IGF-1R levels and enhanced osteo/odontogenic differentiation. Furthermore, the ERK, JNK, and P38 MAPK pathways were significantly inhibited following the overexpression of let-7c in DPMSCs. Deletion of let-7c promoted the activation of the JNK and P38 MAPK pathways. Our cumulative findings indicate that Let-7c can inhibit the osteo/odontogenic differentiation of IGF-1-treated DPMSCs by targeting IGF-1R via the JNK/P38 MAPK signaling pathways. A small non-coding RNA molecule can control transformation of stem cells into bone cells by interrupting growth factor signals. Insulin-like growth factor 1 (IGF-1), the most abundant growth factor in bone, was known to trigger stem cells to transform into bone cells. The microRNA let-7c, primarily known as a tumor suppressor, was also known to be involved in bone generation. However, the interactions between the two molecules were poorly understood. Jinhua Yu at Nanjing Medical University in China and co-workers treated stem cells collected from tooth pulp with let-7c, and then assessed their mineralization, which indicates formation of bone. They found that increasing let-7c concentrations inhibited transformation to bone by blocking the IGF-1 signal. Deletion of let-7c had the opposite effect. These findings may facilitate further research in tooth engineering and bone reconstruction.
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影响因子：
5.6
作者：
Huat TJ;Khan AA;Abdullah JM;Idris FM;Jaafar H
通讯作者：
Jaafar H
影响因子：
3.7
作者：
Joung YH;Lim EJ;Darvin P;Chung SC;Jang JW;Do Park K;Lee HK;Kim HS;Park T;Yang YM
通讯作者：
Yang YM
影响因子：
11.2
作者：
Chien, Chian-Shiu;Wang, Mong-Lien;Chiou, Shih-Hwa
通讯作者：
Chiou, Shih-Hwa
影响因子：
3.7
作者：
Kong D;Heath E;Chen W;Cher ML;Powell I;Heilbrun L;Li Y;Ali S;Sethi S;Hassan O;Hwang C;Gupta N;Chitale D;Sakr WA;Menon M;Sarkar FH
通讯作者：
Sarkar FH
DOI：
10.1007/978-1-4419-1050-9_5
发表时间：
2010-01-01
期刊：
OSTEOIMMUNOLOGY: INTERACTIONS OF THE IMMUNE AND SKELETAL SYSTEMS II
影响因子：
--
作者：
Komori, Toshihisa
通讯作者：
Komori, Toshihisa