Insulin-like growth factor 1 promotes the proliferation and committed differentiation of human dental pulp stem cells through MAPK pathways
Insulin-like growth factor 1 promotes the proliferation and committed differentiation of human dental pulp stem cells through MAPK pathways
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胰岛素样生长因子1通过MAPK途径促进人牙髓干细胞增殖和定向分化
DOI：
10.1016/j.archoralbio.2016.08.011
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发表时间：
2016-12-01
影响因子：
3
通讯作者：
Mu Jinquan
中科院分区：
文献类型：
--
作者：
Lv Taohong;Wu Yongzheng;Mu Jinquan
目的：胰岛素样生长因子1 （IGF-1）是一种广谱生长促进因子，在牙齿自然发育中起关键作用。人牙髓干细胞具有多能性，可影响牙髓和牙本质的修复性再生。本研究旨在探讨IGF-1对人牙髓干细胞增殖分化的影响。方法：从人牙髓中分离纯化hdpsc。随后研究了100ng /ml外源IGF-1处理hdpsc的增殖和成骨/牙源性分化。结果：MTT实验显示IGF-1促进了hDPSCs的增殖。第3 ~ 9天，igf -1处理组ALP活性较对照组明显增强。茜素红染色显示，igf -1处理的细胞含有更多的矿化结节，钙浓度较高。此外，western blot和qRT-PCR分析显示，与未处理的细胞相比，igf -1处理的hdpsc中几种成骨基因（如RUNX2、OSX和OCN）和成牙细胞特异性标志物（DSPP）的表达水平显著上调（P < 0.01）。有趣的是，phospho-ERIC和phospho-p38的表达也上调，表明MAPK信号通路在hDPSCs分化过程中被激活。结论：IGF-1可通过激活MAPK通路促进hDPSCs的增殖和成骨/成牙分化。(C) 2016 Elsevier Ltd.版权所有。
Objectives: Insulin-like growth factor 1 (IGF-1) is a broad-spectrum growth-promoting factor that plays a key role in natural tooth development. Human dental pulp stem cells (hDPSCs) are multipotent and can influence the reparative regeneration of dental pulp and dentin. This study was designed to evaluate the effects of IGF-1 on the proliferation and differentiation of human dental pulp stem cells.Methods: HDPSCs were isolated and purified from human dental pulps. The proliferation and osteo/odontogenic differentiation of hDPSCs treated with 100 ng/ml exogenous IGF-1 were subsequently investigated.Results: MTT assays revealed that IGF-1 enhanced the proliferation of hDPSCs. ALP activity in IGF-1-treated group was obviously enhanced compared to the control group from days 3 to 9. Alizarin red staining revealed that the IGF-1-treated cells contained a greater number of mineralization nodules and had higher calcium concentrations. Moreover, western blot and qRT-PCR analyses demonstrated that the expression levels of several osteogenic genes (e.g., RUNX2, OSX, and OCN) and an odontoblast-specific marker (DSPP) were significantly up-regulated in IGF-1-treated hDPSCs as compared with untreated cells (P < 0.01). Interestingly, the expression of phospho-ERIC and phospho-p38 were also up-regulated, indicating that the MAPK signaling pathway is activated during the differentiation of hDPSCs.Conclusions: IGF-1 can promote the proliferation and osteo/odontogenic differentiation of hDPSCs by activating MAPK pathways. (C) 2016 Elsevier Ltd. All rights reserved.