Rutin protects human periodontal ligament stem cells from TNF-α induced damage to osteogenic differentiation through suppressing mTOR signaling pathway in inflammatory environment

Zhao, Bin; Zhang, Wenjing; Xiong, Yixuan; Zhang, Yunpeng; Jia, Linglu; Xu, Xin

doi:10.1016/j.archoralbio.2019.104584

Cited by 31 publications

(19 citation statements)

References 43 publications

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“…Rutin, a bioflavonoid distributed in fruits and vegetables, was found to significantly enhance the proliferation and osteogenic differentiation of PDLSCs through PI3K/AKT/mTOR signal pathway (Zhao et al, 2020a). In addition, both rutin and another herbal extraction, resveratrol, can protect human PDLSCs from TNF-α-induced damage to osteogenesis (Yuan et al, 2020;Zhao et al, 2020b). The recombinant chimeric protein of angiopoietin-1 (ANG-1) and a short domain of cartilage oligomeric matrix protein (COMP) could also exert the osteogenic role via PI3K/AKT pathway (Kook et al, 2014).…”

Section: Osteogenesismentioning

confidence: 99%

Dental-Derived Mesenchymal Stem Cells: State of the Art

Ouchi

Cao

et al. 2021

Front. Cell Dev. Biol.

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Mesenchymal stem cells (MSCs) could be identified in mammalian teeth. Currently, dental-derived MSCs (DMSCs) has become a collective term for all the MSCs isolated from dental pulp, periodontal ligament, dental follicle, apical papilla, and even gingiva. These DMSCs possess similar multipotent potential as bone marrow-derived MSCs, including differentiation into cells that have the characteristics of odontoblasts, cementoblasts, osteoblasts, chondrocytes, myocytes, epithelial cells, neural cells, hepatocytes, and adipocytes. Besides, DMSCs also have powerful immunomodulatory functions, which enable them to orchestrate the surrounding immune microenvironment. These properties enable DMSCs to have a promising approach in injury repair, tissue regeneration, and treatment of various diseases. This review outlines the most recent advances in DMSCs’ functions and applications and enlightens how these advances are paving the path for DMSC-based therapies.

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Section: Osteogenesismentioning

confidence: 99%

Dental-Derived Mesenchymal Stem Cells: State of the Art

Ouchi

Cao

et al. 2021

Front. Cell Dev. Biol.

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“…52 In addition, they have activities in treating cardiovascular diseases 53 and ischemic stroke, 54 and have anti-inammatory 55 and neuroprotective effects against cerebral ischemia. 56 Rutin had anti-oxidant, 57 anti-carcinogenic, 58 liver protection, 59 anti-inammatory, 60 neuroprotective, 61 and vasoprotective properties. 62 Cinobufagin inhibited PC3 cell growth 63 and had antibrosis properties.…”

Section: Discussionmentioning

confidence: 99%

Identification of blood-activating components from Xueshuan Xinmaining Tablet based on the spectrum–effect relationship and network pharmacology analysis

et al. 2020

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“…4,6 Due to incomplete knowledge of the underlying mechanism, [7][8][9] therapeutic approaches that protect PDLSCs from inflammation-induced dysfunction (eg, reduced stemness and aberrant differentiation) following transplantation are still in their infancy. 10,11 In our previous study, we identified the role of P2X7 receptor (P2X7R) in inflammation-compromised osteogenic differentiation of PDLSCs, and most importantly, we found that the cell impairment could be reversed by P2X7R gene modification. 8 This finding suggests that the transplantation of P2X7R gene-modified PDLSCs could lead to an improved therapeutic outcome.…”

mentioning

confidence: 93%

“…One reason for the lack of success in clinical practice is that PDLSCs are functionally compromised when they are placed in an inflammatory intrabony periodontal defect 4,6 . Due to incomplete knowledge of the underlying mechanism, 7‐9 therapeutic approaches that protect PDLSCs from inflammation‐induced dysfunction (eg, reduced stemness and aberrant differentiation) following transplantation are still in their infancy 10,11 …”

Section: Introductionmentioning

confidence: 99%

Exosomes derived from P2X7 receptor gene-modified cells rescue inflammation-compromised periodontal ligament stem cells from dysfunction

Tian

Xia

et al. 2020

Stem Cells Translational Medicine

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Although cellular therapy has been proposed for inflammation-related disorders such as periodontitis for decades, clinical application has been unsuccessful. One explanation for these disappointing results is that the functions of stem cells are substantially compromised when they are transplanted into an inflammatory in vivo milieu. Considering the previous finding that P2X7 receptor (P2X7R) gene modification is able to reverse inflammation-mediated impairment of periodontal ligament stem cells (PDLSCs), we further hypothesized that cells subjected to P2X7R gene transduction also exert influences on other cells within an in vivo milieu via an exosome-mediated paracrine mechanism. To define the paracrine ability of P2X7R gene-modified cells, P2X7R gene-modified stem cell-derived conditional medium (CM-Ad-P2X7) and exosomes (Exs-Ad-P2X7) were used to incubate PDLSCs. In an inflammatory osteogenic microenvironment, inflammation-mediated changes in PDLSCs were substantially reduced, as shown by quantitative real-time PCR (qRT-PCR) analysis, Western blot analysis, alkaline phosphatase (ALP) staining/activity assays, and Alizarin red staining. In addition, the Agilent miRNA microarray system combined with qRT-PCR analysis revealed that miR-3679-5p, miR-6515-5p, and miR-6747-5p were highly expressed in Exs-Ad-P2X7. Further functional tests and luciferase reporter assays revealed that miR-3679-5p and miR-6747-5p bound directly to the GREM-1 protein, while miR-6515-5p bound to the GREM-1 protein indirectly; these effects combined to rescue inflammation-compromised PDLSCs from dysfunction. Thus, in addition to maintaining their robust functionality under inflammatory conditions, P2X7R genemodified stem cells may exert positive influences on their neighbors via a paracrine mechanism, pointing to a novel strategy for modifying the harsh local microenvironment to accommodate stem cells and promote improved tissue regeneration. Xin-Yue Xu, Bei-Min Tian, and Yu Xia contributed equally to this work.

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Rutin protects human periodontal ligament stem cells from TNF-α induced damage to osteogenic differentiation through suppressing mTOR signaling pathway in inflammatory environment

Cited by 31 publications

References 43 publications

Dental-Derived Mesenchymal Stem Cells: State of the Art

Dental-Derived Mesenchymal Stem Cells: State of the Art

Identification of blood-activating components from Xueshuan Xinmaining Tablet based on the spectrum–effect relationship and network pharmacology analysis

Exosomes derived from P2X7 receptor gene-modified cells rescue inflammation-compromised periodontal ligament stem cells from dysfunction

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