IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla.

IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla.
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IGF-1/IGF-1R/hsa-let-7c轴调节根尖乳头干细胞的定向分化

DOI:
10.1038/srep36922
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发表时间:
2016-11-11
期刊:
影响因子:
4.6
通讯作者:
Yu J
Yu J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ma S;Liu G;Jin L;Pang X;Wang Y;Wang Z;Yu Y;Yu J

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胰岛素样生长因子-1(IGF-1)及其受体IGF-1 R在牙/骨形成中起重要作用,而hsa-let-7积极参与间充质干细胞的成骨分化。然而,IGF-1/IGF-1 R和hsa-let-7之间的相互作用对根尖乳头干细胞(SCAPs)定向分化的影响尚不清楚。在这项研究中,人SCAPs分离和处理IGF-1和hsa-let-7覆盖/低表达病毒。随后研究了这些干细胞的成牙/成骨分化以及丝裂原活化蛋白激酶(MAPK)通路的参与。茜素红染色结果显示,hsa-let-7 clow表达能显著促进IGF-1处理的SCAPs的矿化,hsa-let-7 cover表达能显著减少IGF-1处理的SCAPs的钙沉积。Western blot和real-time RT-PCR进一步证实IGF-1处理后的SCAPs中ALP、RUNX 2/RUNX 2、OSX/OSX、OCN/OCN、COL-I/COL-I、DSPP/DSP和BMP-1/BMP-1的表达显著上调。相反,hsa-let-7 cover-表达可下调这些成牙/成骨标志物的表达。Western blot结果显示,JNK和p38 MAPK信号通路在低浓度的SCAP中被激活,而在高浓度的SCAP中被抑制。IGF-1/IGF-1 R/hsa-let-7 caxis可通过调控JNK和p38 MAPK信号通路共同调控IGF-1处理的SCAPs的牙/成骨分化。
Insulin-like growth factor-1 (IGF-1) and its receptor IGF-1R play a paramount role in tooth/bone formation whilehsa-let-7cactively participates in the osteogenic differentiation of mesenchymal stem cells. However, the interaction between IGF-1/IGF-1R andhsa-let-7con the committed differentiation of stem cells from apical papilla (SCAPs) remains unclear. In this study, human SCAPs were isolated and treated with IGF-1 andhsa-let-7cover/low-expression viruses. The odonto/osteogenic differentiation of these stem cells and the involvement of mitogen-activated protein kinase (MAPK) pathway were subsequently investigated. Alizarin red staining showed thathsa-let-7clow-expression can significantly promote the mineralization of IGF-1 treated SCAPs, whilehsa-let-7cover-expression can decrease the calcium deposition of IGF-1 treated SCAPs. Western blot assay and real-time reverse transcription polymerase chain reaction further demonstrated that the expression of odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, COL-I/COL-I, DSPP/DSP, and DMP-1/DMP-1) in IGF-1 treated SCAPs were significantly upregulated inLet-7c-low group. On the contrary,hsa-let-7cover-expression could downregulate the expression of these odonto/osteogenic markers. Moreover, western blot assay showed that the JNK and p38 MAPK signaling pathways were activated inLet-7c-low SCAPs but inhibited inLet-7c-over SCAPs. Together, the IGF-1/IGF-1R/hsa-let-7caxis can control the odonto/osteogenic differentiation of IGF-1-treated SCAPs via the regulation of JNK and p38 MAPK signaling pathways.
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