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机械应力通过Wnt/β-连环蛋白信号通路调节牙周膜干细胞的成骨分化及RANKL/OPG比值。

Mechanical stress regulates osteogenic differentiation and RANKL/OPG ratio in periodontal ligament stem cells by the Wnt/β-catenin pathway.

作者信息

Zhang Liqiang, Liu Wenjia, Zhao Jiangdong, Ma Xiaojie, Shen Lin, Zhang Yongjie, Jin Fang, Jin Yan

机构信息

MS-State Key Laboratory, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China; Institute for Tissue Engineering and Regenerative Medicine Research of Xi'an, Shaanxi 710032, People's Republic of China.

Department of Aerospace Biodynamics, Faculty of Aerospace Medicine, The Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.

出版信息

Biochim Biophys Acta. 2016 Oct;1860(10):2211-9. doi: 10.1016/j.bbagen.2016.05.003. Epub 2016 May 3.

Abstract

BACKGROUND

The balance between osteoblastic and osteoclastic activity is critical in orthodontic tooth movement (OTM). Mesenchymal stem cells (MSCs) play an important role in maintaining bone homeostasis, and periodontal ligament stem cells (PDLSCs) are tissue-specific MSCs in the periodontal ligament. However, whether PDLSCs are required for periodontal tissue remodeling during OTM is not fully understood.

METHODS

Here, we used PDGFRα and Nestin to trace PDLSCs during OTM in rats. We treat human PDLSCs with 100kpa static pressure for 1h or 12h in vitro, and examined the phenotypic changes and expression of RANKL and OPG in these cells.

RESULTS

In vivo, we found that positive signals of PDGFRα and Nestin in the PDL gradually increased and then decreased on the pressure side to which pressure was applied. In vitro, the osteogenic differentiation of PDLSCs was significantly increased after force treatment for 1h relative to 12h. In contrast, the expression ratio of RANKL/OPG was reduced at 1h and significantly increased at 12h. Furthermore, we found that the Wnt/β-catenin pathway was dynamically activated in the PDL and in PDLSCs after mechanical stimulation. Importantly, the canonical Wnt pathway inhibitor DKK1 blocked the osteogenesis effect and rescued the ratio of RANKL/OPG in PDLSCs under force treatment for 1h.

CONCLUSIONS

Our findings reveal that PDLSCs participate in OTM and that the Wnt/β-catenin pathway maintains bone homeostasis during tooth movement by regulating the balance between osteoblastic and osteoclastic activity.

GENERAL SIGNIFICANCE

We describe a novel potential mechanism related to tooth movement.

摘要

背景

成骨细胞与破骨细胞活性之间的平衡在正畸牙齿移动(OTM)中至关重要。间充质干细胞(MSC)在维持骨稳态中发挥重要作用,而牙周膜干细胞(PDLSC)是牙周膜中的组织特异性MSC。然而,在OTM过程中牙周组织重塑是否需要PDLSC尚未完全明确。

方法

在此,我们在大鼠OTM过程中使用血小板衍生生长因子受体α(PDGFRα)和巢蛋白(Nestin)来追踪PDLSC。我们在体外对人PDLSC施加100千帕斯卡(kpa)静压力1小时或12小时,并检测这些细胞的表型变化以及核因子κB受体活化因子配体(RANKL)和骨保护素(OPG)的表达。

结果

在体内,我们发现PDL中PDGFRα和Nestin的阳性信号在施加压力的压力侧逐渐增加,然后下降。在体外,与12小时相比,PDLSC在受力处理1小时后的成骨分化显著增加。相反,RANKL/OPG的表达比率在1小时时降低,在12小时时显著增加。此外,我们发现机械刺激后,Wnt/β-连环蛋白通路在PDL和PDLSC中被动态激活。重要的是,经典Wnt通路抑制剂DKK1阻断了成骨作用,并挽救了受力处理1小时的PDLSC中RANKL/OPG的比率。

结论

我们的研究结果表明,PDLSC参与OTM,并且Wnt/β-连环蛋白通路通过调节成骨细胞与破骨细胞活性之间的平衡在牙齿移动过程中维持骨稳态。

一般意义

我们描述了一种与牙齿移动相关的新的潜在机制。

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