Enhancing osteogenic potential of hDPSCs by resveratrol through reducing oxidative stress via the Sirt1/Nrf2 pathway

The osteogenic potential of the human dental pulp stromal cells (hDPSCs) was reduced in the state of oxidative stress. Resveratrol (RSV) possesses numerous biological properties, including osteogenic potential, growth-promoting and antioxidant activities. This study investigates the osteogenic poten...

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Veröffentlicht in:Pharmaceutical biology 2022-12, Vol.60 (1), p.501-508
Hauptverfasser: Zhang, Jingying, Li, Rui, Man, Kenny, Yang, Xuebin B.
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Yang, Xuebin B.
description The osteogenic potential of the human dental pulp stromal cells (hDPSCs) was reduced in the state of oxidative stress. Resveratrol (RSV) possesses numerous biological properties, including osteogenic potential, growth-promoting and antioxidant activities. This study investigates the osteogenic potential of RSV by activating the Sirt1/Nrf2 pathway on oxidatively stressed hDPSCs and old mice. The hDPSCs were subjected to reactive oxygen species (ROS) fluorescence staining, cell proliferation assay, ROS activity assay, superoxide dismutase (SOD) enzyme activity, the glutathione (GSH) concentration assay, alkaline phosphatase staining, real-time polymerase chain reaction (RT-PCR) and Sirt1 immunofluorescence labelling to assess the antioxidant stress and osteogenic ability of RSV. Forty female Kunming mice were divided into Old, Old-RSV, Young and Young-RSV groups to assess the repair of calvarial defects of 0.2 mL RSV of 20 mg/kg/d for seven days by injecting intraperitoneally at 4 weeks after surgery using micro-computed tomography, nonlinear optical microscope and immunohistochemical analysis. RSV abates oxidative stress by alleviating the proliferation, mitigating the ROS activity, increasing the SOD enzyme activity and ameliorating the GSH concentration (RSV IC 50 in hDPSCs is 67.65 ± 9.86). The antioxidative stress and osteogenic capabilities of RSV were confirmed by the up-regulated gene expression of SOD1, xCT, RUNX2 and OCN, as well as Sirt1/Nrf2. The collagen, bone matrix formation and Sirt1 expression, are significantly increased after RSV treatment in mice. For elderly or patients with oxidative stress physiological states such as hypertension, heart disease, diabetes, etc., RSV may potentially improve bone augmentation surgery in regenerative medicine.
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Resveratrol (RSV) possesses numerous biological properties, including osteogenic potential, growth-promoting and antioxidant activities. This study investigates the osteogenic potential of RSV by activating the Sirt1/Nrf2 pathway on oxidatively stressed hDPSCs and old mice. The hDPSCs were subjected to reactive oxygen species (ROS) fluorescence staining, cell proliferation assay, ROS activity assay, superoxide dismutase (SOD) enzyme activity, the glutathione (GSH) concentration assay, alkaline phosphatase staining, real-time polymerase chain reaction (RT-PCR) and Sirt1 immunofluorescence labelling to assess the antioxidant stress and osteogenic ability of RSV. Forty female Kunming mice were divided into Old, Old-RSV, Young and Young-RSV groups to assess the repair of calvarial defects of 0.2 mL RSV of 20 mg/kg/d for seven days by injecting intraperitoneally at 4 weeks after surgery using micro-computed tomography, nonlinear optical microscope and immunohistochemical analysis. RSV abates oxidative stress by alleviating the proliferation, mitigating the ROS activity, increasing the SOD enzyme activity and ameliorating the GSH concentration (RSV IC 50 in hDPSCs is 67.65 ± 9.86). The antioxidative stress and osteogenic capabilities of RSV were confirmed by the up-regulated gene expression of SOD1, xCT, RUNX2 and OCN, as well as Sirt1/Nrf2. The collagen, bone matrix formation and Sirt1 expression, are significantly increased after RSV treatment in mice. For elderly or patients with oxidative stress physiological states such as hypertension, heart disease, diabetes, etc., RSV may potentially improve bone augmentation surgery in regenerative medicine.</description><identifier>ISSN: 1388-0209</identifier><identifier>EISSN: 1744-5116</identifier><identifier>DOI: 10.1080/13880209.2022.2037664</identifier><identifier>PMID: 35188840</identifier><language>eng</language><publisher>England: Taylor &amp; Francis</publisher><subject>Age Factors ; Alkaline phosphatase ; Animals ; Animals, Outbred Strains ; Antioxidants ; Bone growth ; Bone matrix ; Bone surgery ; Cbfa-1 protein ; Cell proliferation ; Cell Proliferation - drug effects ; Cells, Cultured ; Collagen ; Computed tomography ; Dental pulp ; Dental Pulp - cytology ; Dental pulp stromal cell ; Diabetes mellitus ; Enzymatic activity ; Enzymes ; Female ; Gene expression ; Glutathione ; Heart diseases ; Humans ; Immunofluorescence ; Labeling ; Mice ; NF-E2-Related Factor 2 - metabolism ; OCN ; Osteogenesis - drug effects ; Oxidative stress ; Oxidative Stress - drug effects ; Polymerase chain reaction ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Regenerative medicine ; Resveratrol ; Resveratrol - pharmacology ; ROS ; RUNX1 ; SIRT1 protein ; Sirtuin 1 - metabolism ; skull defect ; SOD ; Stromal cells ; Stromal Cells - cytology ; Stromal Cells - drug effects ; Superoxide dismutase ; Superoxide Dismutase - metabolism ; xCT</subject><ispartof>Pharmaceutical biology, 2022-12, Vol.60 (1), p.501-508</ispartof><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor &amp; Francis Group. 2022</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor &amp; Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 The Author(s). 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Resveratrol (RSV) possesses numerous biological properties, including osteogenic potential, growth-promoting and antioxidant activities. This study investigates the osteogenic potential of RSV by activating the Sirt1/Nrf2 pathway on oxidatively stressed hDPSCs and old mice. The hDPSCs were subjected to reactive oxygen species (ROS) fluorescence staining, cell proliferation assay, ROS activity assay, superoxide dismutase (SOD) enzyme activity, the glutathione (GSH) concentration assay, alkaline phosphatase staining, real-time polymerase chain reaction (RT-PCR) and Sirt1 immunofluorescence labelling to assess the antioxidant stress and osteogenic ability of RSV. Forty female Kunming mice were divided into Old, Old-RSV, Young and Young-RSV groups to assess the repair of calvarial defects of 0.2 mL RSV of 20 mg/kg/d for seven days by injecting intraperitoneally at 4 weeks after surgery using micro-computed tomography, nonlinear optical microscope and immunohistochemical analysis. RSV abates oxidative stress by alleviating the proliferation, mitigating the ROS activity, increasing the SOD enzyme activity and ameliorating the GSH concentration (RSV IC 50 in hDPSCs is 67.65 ± 9.86). The antioxidative stress and osteogenic capabilities of RSV were confirmed by the up-regulated gene expression of SOD1, xCT, RUNX2 and OCN, as well as Sirt1/Nrf2. The collagen, bone matrix formation and Sirt1 expression, are significantly increased after RSV treatment in mice. For elderly or patients with oxidative stress physiological states such as hypertension, heart disease, diabetes, etc., RSV may potentially improve bone augmentation surgery in regenerative medicine.</description><subject>Age Factors</subject><subject>Alkaline phosphatase</subject><subject>Animals</subject><subject>Animals, Outbred Strains</subject><subject>Antioxidants</subject><subject>Bone growth</subject><subject>Bone matrix</subject><subject>Bone surgery</subject><subject>Cbfa-1 protein</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Collagen</subject><subject>Computed tomography</subject><subject>Dental pulp</subject><subject>Dental Pulp - cytology</subject><subject>Dental pulp stromal cell</subject><subject>Diabetes mellitus</subject><subject>Enzymatic activity</subject><subject>Enzymes</subject><subject>Female</subject><subject>Gene expression</subject><subject>Glutathione</subject><subject>Heart diseases</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Labeling</subject><subject>Mice</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>OCN</subject><subject>Osteogenesis - drug effects</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Polymerase chain reaction</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Regenerative medicine</subject><subject>Resveratrol</subject><subject>Resveratrol - pharmacology</subject><subject>ROS</subject><subject>RUNX1</subject><subject>SIRT1 protein</subject><subject>Sirtuin 1 - metabolism</subject><subject>skull defect</subject><subject>SOD</subject><subject>Stromal cells</subject><subject>Stromal Cells - cytology</subject><subject>Stromal Cells - drug effects</subject><subject>Superoxide dismutase</subject><subject>Superoxide Dismutase - metabolism</subject><subject>xCT</subject><issn>1388-0209</issn><issn>1744-5116</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNp9ks1u1DAUhSMEoqXwCCBLbNiktZ3YcTYINBSoVAFSu7du_DPxKBMPtjNl3h6HTCvKgo19df2dY_vqFMVrgs8JFviCVEJgittziinNS9VwXj8pTklT1yUjhD_NdWbKGTopXsS4wRizqmLPi5OKESFEjU-LdDn2MCo3rpGPyfi1GZ1CO5_MmBwMyFvUf_pxs4qoO6Bg4t4ESMEPKPXBT-s-9_S0yH85DcntDYopgxHtHWTKoBsXErn4FixFO0j9HRxeFs8sDNG8Ou5nxe3ny9vV1_L6-5er1cfrUjFOUwmaYNK1GoxlhNHW8soIzRnj1opaaFZRarmqRSs6q5RoO8Ib0LxrbU05r86Kq8VWe9jIXXBbCAfpwck_DR_WEkJyajBSGQ6EA8bG8BrXpiO6Yxx00-JcqTZ7vV-8dlO3NVrl8QQYHpk-PhldL9d-L4XgDLezwbujQfA_JxOT3LqozDDAaPwUJeUVyShhTUbf_oNu_BTGPClJG05qSlsyU2yhVPAxBmMfHkOwnCMi7yMi54jIY0Sy7s3fP3lQ3WciAx8WwI3Why3c-TBomeAw-GDDHJYoq__f8RvT_s0G</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Zhang, Jingying</creator><creator>Li, Rui</creator><creator>Man, Kenny</creator><creator>Yang, Xuebin B.</creator><general>Taylor &amp; 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Li, Rui ; Man, Kenny ; Yang, Xuebin B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-ad101b9daef51529f63e8d6556ff848d5322f6c4898bfcc89b167ad6b9f42663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Age Factors</topic><topic>Alkaline phosphatase</topic><topic>Animals</topic><topic>Animals, Outbred Strains</topic><topic>Antioxidants</topic><topic>Bone growth</topic><topic>Bone matrix</topic><topic>Bone surgery</topic><topic>Cbfa-1 protein</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Collagen</topic><topic>Computed tomography</topic><topic>Dental pulp</topic><topic>Dental Pulp - cytology</topic><topic>Dental pulp stromal cell</topic><topic>Diabetes mellitus</topic><topic>Enzymatic activity</topic><topic>Enzymes</topic><topic>Female</topic><topic>Gene expression</topic><topic>Glutathione</topic><topic>Heart diseases</topic><topic>Humans</topic><topic>Immunofluorescence</topic><topic>Labeling</topic><topic>Mice</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>OCN</topic><topic>Osteogenesis - drug effects</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Polymerase chain reaction</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Regenerative medicine</topic><topic>Resveratrol</topic><topic>Resveratrol - pharmacology</topic><topic>ROS</topic><topic>RUNX1</topic><topic>SIRT1 protein</topic><topic>Sirtuin 1 - metabolism</topic><topic>skull defect</topic><topic>SOD</topic><topic>Stromal cells</topic><topic>Stromal Cells - cytology</topic><topic>Stromal Cells - drug effects</topic><topic>Superoxide dismutase</topic><topic>Superoxide Dismutase - metabolism</topic><topic>xCT</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Jingying</creatorcontrib><creatorcontrib>Li, Rui</creatorcontrib><creatorcontrib>Man, Kenny</creatorcontrib><creatorcontrib>Yang, Xuebin B.</creatorcontrib><collection>Taylor &amp; 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Resveratrol (RSV) possesses numerous biological properties, including osteogenic potential, growth-promoting and antioxidant activities. This study investigates the osteogenic potential of RSV by activating the Sirt1/Nrf2 pathway on oxidatively stressed hDPSCs and old mice. The hDPSCs were subjected to reactive oxygen species (ROS) fluorescence staining, cell proliferation assay, ROS activity assay, superoxide dismutase (SOD) enzyme activity, the glutathione (GSH) concentration assay, alkaline phosphatase staining, real-time polymerase chain reaction (RT-PCR) and Sirt1 immunofluorescence labelling to assess the antioxidant stress and osteogenic ability of RSV. Forty female Kunming mice were divided into Old, Old-RSV, Young and Young-RSV groups to assess the repair of calvarial defects of 0.2 mL RSV of 20 mg/kg/d for seven days by injecting intraperitoneally at 4 weeks after surgery using micro-computed tomography, nonlinear optical microscope and immunohistochemical analysis. RSV abates oxidative stress by alleviating the proliferation, mitigating the ROS activity, increasing the SOD enzyme activity and ameliorating the GSH concentration (RSV IC 50 in hDPSCs is 67.65 ± 9.86). The antioxidative stress and osteogenic capabilities of RSV were confirmed by the up-regulated gene expression of SOD1, xCT, RUNX2 and OCN, as well as Sirt1/Nrf2. The collagen, bone matrix formation and Sirt1 expression, are significantly increased after RSV treatment in mice. For elderly or patients with oxidative stress physiological states such as hypertension, heart disease, diabetes, etc., RSV may potentially improve bone augmentation surgery in regenerative medicine.</abstract><cop>England</cop><pub>Taylor &amp; Francis</pub><pmid>35188840</pmid><doi>10.1080/13880209.2022.2037664</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7971-7180</orcidid><oa>free_for_read</oa></addata></record>
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subjects Age Factors
Alkaline phosphatase
Animals
Animals, Outbred Strains
Antioxidants
Bone growth
Bone matrix
Bone surgery
Cbfa-1 protein
Cell proliferation
Cell Proliferation - drug effects
Cells, Cultured
Collagen
Computed tomography
Dental pulp
Dental Pulp - cytology
Dental pulp stromal cell
Diabetes mellitus
Enzymatic activity
Enzymes
Female
Gene expression
Glutathione
Heart diseases
Humans
Immunofluorescence
Labeling
Mice
NF-E2-Related Factor 2 - metabolism
OCN
Osteogenesis - drug effects
Oxidative stress
Oxidative Stress - drug effects
Polymerase chain reaction
Reactive oxygen species
Reactive Oxygen Species - metabolism
Regenerative medicine
Resveratrol
Resveratrol - pharmacology
ROS
RUNX1
SIRT1 protein
Sirtuin 1 - metabolism
skull defect
SOD
Stromal cells
Stromal Cells - cytology
Stromal Cells - drug effects
Superoxide dismutase
Superoxide Dismutase - metabolism
xCT
title Enhancing osteogenic potential of hDPSCs by resveratrol through reducing oxidative stress via the Sirt1/Nrf2 pathway
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