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Effects of rutin on the oxidative stress, proliferation and osteogenic differentiation of periodontal ligament stem cells in LPS-induced inflammatory environment and the underlying mechanism

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Abstract

Periodontitis can cause damage to dental support tissue and affect the function of periodontal ligament cells. Rutin, a common flavonoid, plays a key role in anti-inflammatory responses, tissue repair and bone development. The purpose of this study was to investigate the effects of rutin on the oxidative stress, proliferation, and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) in an inflammatory environment and the underlying mechanism. Lipopolysaccharide (LPS) was used to stimulate PDLSCs to mimic an inflammatory environment model. Reactive oxygen species (ROS) levels were detected by the dichlorodihydrofluorescein diacetate (DCFH-DA) probe and the oxidative stress factors were tested by an oxidative stress factor detection kit. Moreover, the proliferation of PDLSCs was evaluated by cell counting kit-8 (CCK-8) assay. In addition, the osteogenic differentiation of PDLSCs was determined by alkaline phosphatase (ALP) staining, ALP activity test, alizarin red staining, and alizarin red semi-quantitative analysis. Furthermore, the protein levels of AKT and p-AKT were detected by Western blot. The results showed that rutin inhibited the release of ROS and increased the secretion of oxidative stress factors [superoxide dismutase (SOD) and glutathione (GSH)] and promoted the proliferation of PDLSCs in an inflammatory environment. Moreover, rutin upregulated ALP activity and enhanced the number of mineralized nodules. Conversely, the use of LY294002 (an inhibitor of PI3K) blocked the activation of the PI3K/AKT signaling pathway and prevented the beneficial effects of rutin. In conclusion, rutin promoted the antioxidative stress ability, proliferation and osteogenic differentiation of PDLSCs through PI3K/AKT signaling pathway in LPS-induced inflammatory environment.

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Acknowledgements

This work was supported by the Construction Engineering Special Fund of Taishan Scholars (Grant Number ts201511106), Natural Science Foundation of Shandong Province (Grant Number ZR2017MH031), and Fundamental Research Funds of Shandong University (Grant Number 2018GN024).

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Author notes

  1. Bin Zhao and Wenjing Zhang have contributed equally to this study.

Authors and Affiliations

  1. Department of Oral Implantology, School and Hospital of Stomatology, Shandong University, No. 44-1, Wenhua Xi Road, Jinan, 250012, Shandong, China

    Bin Zhao, Wenjing Zhang, Yixuan Xiong, Yunpeng Zhang, Dongjiao Zhang & Xin Xu

  2. Shandong Key Laboratory of Oral Tissue Regeneration, Jinan, China

    Bin Zhao, Wenjing Zhang, Yixuan Xiong, Yunpeng Zhang, Dongjiao Zhang & Xin Xu

  3. Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China

    Bin Zhao, Wenjing Zhang, Yixuan Xiong, Yunpeng Zhang, Dongjiao Zhang & Xin Xu

  4. Department of Oral Implantology, The Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China

    Yunpeng Zhang

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  1. Bin Zhao
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Correspondence to Dongjiao Zhang or Xin Xu.

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Zhao, B., Zhang, W., Xiong, Y. et al. Effects of rutin on the oxidative stress, proliferation and osteogenic differentiation of periodontal ligament stem cells in LPS-induced inflammatory environment and the underlying mechanism. J Mol Hist 51, 161–171 (2020). https://doi.org/10.1007/s10735-020-09866-9

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  • DOI: https://doi.org/10.1007/s10735-020-09866-9

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