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mTor 在成牙本质细胞分化中发挥重要作用。

mTor plays an important role in odontoblast differentiation.

机构信息

Department of Biology and Materials Sciences, University of Michigan, School of Dentistry, Ann Arbor, Michigan, USA.

出版信息

J Endod. 2011 Aug;37(8):1081-5. doi: 10.1016/j.joen.2011.03.034. Epub 2011 May 28.

Abstract

INTRODUCTION

Signaling pathways responsible for dentin regeneration in a dental pulp are not fully understood. In this study, we determined the effects of the mammalian target of rapamycin (mTor) on the differentiation and mineralization of dental pulp stem cells. We hypothesized that the two known mTor complexes Torc1 and Torc 2 play pivotal roles in the differentiation of odontoblasts and that they modulate deposition of a mineralized extracellular matrix. Therefore, we investigated the effects of Torc1 and Torc 2 signaling on the differentiation and mineralization of stem cells from human exfoliated deciduous teeth (SHED).

METHODS

We used Western blot analysis to examine the expression of markers of dental differentiation in SHED (+/-) inhibition of either Torc1 or Torc 2 complex proteins raptor or rictor, respectively. In addition, the deposition of a mineralized matrix was determined under these conditions via alkaline phosphatase and alizarin red staining.

RESULTS

Results show that the inhibition of Torc 1, via reduced expression of either raptor or mTor, severely restricts the synthesis of dentin sialoprotein and inhibits deposition of a mineralized matrix. Inhibition of Torc 2, via reduction of rictor, has the opposite effect, enhancing mineralization. This latter effect disappears when both rictor and mTor are inhibited, showing that the Torc 2 effect is Torc 1 dependent.

CONCLUSIONS

These results strongly suggest an important role for mTor in dental pulp stem cell differentiation and provide evidence that the mechanisms involved in protein synthesis could prove an interesting target for dental pulp tissue engineering.

摘要

简介

负责牙髓内牙本质再生的信号通路尚未完全阐明。在这项研究中,我们确定了哺乳动物雷帕霉素靶蛋白(mTor)对牙髓干细胞分化和矿化的影响。我们假设两个已知的 mTor 复合物 Torc1 和 Torc2 在成牙本质细胞分化中发挥关键作用,并且它们调节矿化细胞外基质的沉积。因此,我们研究了 Torc1 和 Torc2 信号对人乳牙脱落牙髓干细胞(SHED)分化和矿化的影响。

方法

我们使用 Western blot 分析来检测 SHED 中牙分化标志物的表达,(+/-)分别抑制 Torc1 或 Torc2 复合物蛋白 Raptor 或 Rictor。此外,在这些条件下通过碱性磷酸酶和茜素红染色来确定矿化基质的沉积。

结果

结果表明,通过降低 Raptor 或 mTor 的表达抑制 Torc1,严重限制了牙本质涎蛋白的合成,并抑制了矿化基质的沉积。通过减少 Rictor 抑制 Torc2 会产生相反的效果,增强矿化。当同时抑制 Rictor 和 mTor 时,这种后一种效果消失,表明 Torc2 效应依赖于 Torc1。

结论

这些结果强烈表明 mTor 在牙髓干细胞分化中起重要作用,并提供了证据表明涉及蛋白质合成的机制可能成为牙髓组织工程的一个有趣靶点。

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