Metformin combats high glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells via inhibition of the NPR3-mediated ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-07-15

AUTHORS

Yi-Lin Zhang, Fen Liu, Zhi-Bang Li, Xiao-Tao He, Xuan Li, Rui-Xin Wu, Hai-Hua Sun, Shao-Hua Ge, Fa-Ming Chen, Ying An

ABSTRACT

BackgroundHigh glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) has long been a challenge to periodontal regeneration for diabetic individuals. Metformin is an anti-hyperglycemic drug that exhibits abundant biological activities associated with cell metabolism and downstream tissue regeneration. However, how metformin combats damage to PDLSC osteogenic differentiation under high glucose and the underlying mechanisms remain unknown.MethodsOsteogenic differentiation of PDLSCs was assessed by alkaline phosphatase (ALP) staining, ALP activity, Alizarin Red staining and quantitative assay, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. RNA-seq analysis was performed to screen target genes of metformin, and the effects of target genes were confirmed using lentivirus transfection. Western blot analysis was also used to detect the protein level of underlying signaling pathways.ResultsWe found that osteogenic differentiation of PDLSCs under high glucose was decreased, and metformin addition enhanced this capacity of differentiation. Furthermore, the results of RNA-seq analysis showed that natriuretic peptide receptor 3 (NPR3) was upregulated in PDLSCs under high glucose and downregulated after metformin addition. When the underlying pathways involved were investigated, we found that upregulation of NPR3 can compromise the metformin-enhanced PDLSC osteogenic differentiation and activate the MAPK pathway (especially the p38 MAPK and Erk1/2 pathway), and that inhibition of the NPR3-mediated p38 MAPK or Erk1/2 pathway enhanced the osteogenic differentiation of PDLSCs under high glucose.ConclusionsThe present study suggests that metformin may enhance the osteogenic differentiation of PDLSCs under high glucose via downregulation of NPR3 and inhibition of its downstream MAPK pathway. This is the first report identifying the involvement of NPR3-mediated MAPK pathway in the metformin-enhanced osteogenic differentiation, indicating that NPR3 antagonists, such as metformin, may be feasible therapeutics for periodontal tissue regeneration in diabetic individuals. More... »

PAGES

305

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13287-022-02992-z

DOI

http://dx.doi.org/10.1186/s13287-022-02992-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1149508665

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35841070


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Differentiation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Proliferation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cells, Cultured", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Glucose", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "MAP Kinase Signaling System", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Metformin", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Osteogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Periodontal Ligament", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptors, Atrial Natriuretic Factor", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Stem Cells", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "p38 Mitogen-Activated Protein Kinases", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China", 
          "id": "http://www.grid.ac/institutes/grid.233520.5", 
          "name": [
            "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zhang", 
        "givenName": "Yi-Lin", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Stomatology Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an, Shaanxi, People\u2019s Republic of China", 
          "id": "http://www.grid.ac/institutes/grid.440257.0", 
          "name": [
            "Department of Stomatology Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an, Shaanxi, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Liu", 
        "givenName": "Fen", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China", 
          "id": "http://www.grid.ac/institutes/grid.233520.5", 
          "name": [
            "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Li", 
        "givenName": "Zhi-Bang", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China", 
          "id": "http://www.grid.ac/institutes/grid.233520.5", 
          "name": [
            "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "He", 
        "givenName": "Xiao-Tao", 
        "id": "sg:person.016264044545.43", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016264044545.43"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China", 
          "id": "http://www.grid.ac/institutes/grid.233520.5", 
          "name": [
            "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Li", 
        "givenName": "Xuan", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China", 
          "id": "http://www.grid.ac/institutes/grid.233520.5", 
          "name": [
            "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wu", 
        "givenName": "Rui-Xin", 
        "id": "sg:person.0674130045.27", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0674130045.27"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China", 
          "id": "http://www.grid.ac/institutes/grid.233520.5", 
          "name": [
            "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sun", 
        "givenName": "Hai-Hua", 
        "id": "sg:person.0623606063.33", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0623606063.33"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China", 
          "id": "http://www.grid.ac/institutes/grid.27255.37", 
          "name": [
            "Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ge", 
        "givenName": "Shao-Hua", 
        "id": "sg:person.014455403635.21", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014455403635.21"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China", 
          "id": "http://www.grid.ac/institutes/grid.233520.5", 
          "name": [
            "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chen", 
        "givenName": "Fa-Ming", 
        "id": "sg:person.0651505472.53", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0651505472.53"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China", 
          "id": "http://www.grid.ac/institutes/grid.233520.5", 
          "name": [
            "State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi\u2019an, People\u2019s Republic of China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "An", 
        "givenName": "Ying", 
        "id": "sg:person.016436034605.27", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016436034605.27"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1007/s00018-012-0983-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051360008", 
          "https://doi.org/10.1007/s00018-012-0983-8"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13287-021-02322-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1137601306", 
          "https://doi.org/10.1186/s13287-021-02322-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41574-019-0242-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1120494863", 
          "https://doi.org/10.1038/s41574-019-0242-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/ar4253", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042771043", 
          "https://doi.org/10.1186/ar4253"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s12015-018-9869-y", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1111651697", 
          "https://doi.org/10.1007/s12015-018-9869-y"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41418-020-0593-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1129565834", 
          "https://doi.org/10.1038/s41418-020-0593-1"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13287-021-02618-w", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1141971507", 
          "https://doi.org/10.1186/s13287-021-02618-w"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrendo.2011.106", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034661192", 
          "https://doi.org/10.1038/nrendo.2011.106"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nri2395", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034703692", 
          "https://doi.org/10.1038/nri2395"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2022-07-15", 
    "datePublishedReg": "2022-07-15", 
    "description": "BackgroundHigh glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) has long been a challenge to periodontal regeneration for diabetic individuals. Metformin is an anti-hyperglycemic drug that exhibits abundant biological activities associated with cell metabolism and downstream tissue regeneration. However, how metformin combats damage to PDLSC osteogenic differentiation under high glucose and the underlying mechanisms remain unknown.MethodsOsteogenic differentiation of PDLSCs was assessed by alkaline phosphatase (ALP) staining, ALP activity, Alizarin Red staining and quantitative assay, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. RNA-seq analysis was performed to screen target genes of metformin, and the effects of target genes were confirmed using lentivirus transfection. Western blot analysis was also used to detect the protein level of underlying signaling pathways.ResultsWe found that osteogenic differentiation of PDLSCs under high glucose was decreased, and metformin addition enhanced this capacity of differentiation. Furthermore, the results of RNA-seq analysis showed that natriuretic peptide receptor 3 (NPR3) was upregulated in PDLSCs under high glucose and downregulated after metformin addition. When the underlying pathways involved were investigated, we found that upregulation of NPR3 can compromise the metformin-enhanced PDLSC osteogenic differentiation and activate the MAPK pathway (especially the p38 MAPK and Erk1/2 pathway), and that inhibition of the NPR3-mediated p38 MAPK or Erk1/2 pathway enhanced the osteogenic differentiation of PDLSCs\u00a0under high glucose.ConclusionsThe present study suggests that metformin may enhance the osteogenic differentiation of PDLSCs under high glucose via downregulation of NPR3 and inhibition of its downstream MAPK pathway. This is the first report identifying the involvement of NPR3-mediated MAPK pathway in the metformin-enhanced osteogenic differentiation, indicating that NPR3 antagonists, such as metformin, may be feasible therapeutics for periodontal tissue regeneration in diabetic individuals.", 
    "genre": "article", 
    "id": "sg:pub.10.1186/s13287-022-02992-z", 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1043222", 
        "issn": [
          "1757-6512"
        ], 
        "name": "Stem Cell Research & Therapy", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "13"
      }
    ], 
    "keywords": [
      "periodontal ligament stem cells", 
      "natriuretic peptide receptor 3", 
      "glucose-induced damage", 
      "human periodontal ligament stem cells", 
      "high glucose", 
      "Western blot analysis", 
      "metformin addition", 
      "diabetic individuals", 
      "MAPK pathway", 
      "PDLSC osteogenic differentiation", 
      "high glucose-induced damage", 
      "anti-hyperglycemic drugs", 
      "real-time polymerase chain reaction", 
      "quantitative real-time polymerase chain reaction", 
      "blot analysis", 
      "ConclusionsThe present study", 
      "stem cells", 
      "osteogenic differentiation", 
      "feasible therapeutics", 
      "downstream MAPK pathway", 
      "underlying signaling pathways", 
      "capacity of differentiation", 
      "polymerase chain reaction", 
      "metformin", 
      "periodontal tissue regeneration", 
      "lentivirus transfection", 
      "receptor 3", 
      "RNA-seq analysis", 
      "target genes", 
      "ERK1/2 pathway", 
      "periodontal regeneration", 
      "alizarin red staining", 
      "protein levels", 
      "p38 MAPK", 
      "chain reaction", 
      "red staining", 
      "underlying mechanism", 
      "phosphatase staining", 
      "alkaline phosphatase staining", 
      "signaling pathways", 
      "abundant biological activities", 
      "glucose", 
      "inhibition", 
      "tissue regeneration", 
      "present study", 
      "staining", 
      "ALP activity", 
      "cell metabolism", 
      "pathway", 
      "first report", 
      "differentiation", 
      "damage", 
      "cells", 
      "antagonist", 
      "individuals", 
      "biological activity", 
      "ResultsWe", 
      "upregulation", 
      "drugs", 
      "downregulation", 
      "regeneration", 
      "therapeutics", 
      "activity", 
      "genes", 
      "MAPK", 
      "metabolism", 
      "involvement", 
      "report", 
      "transfection", 
      "analysis", 
      "levels", 
      "addition", 
      "study", 
      "effect", 
      "mechanism", 
      "results", 
      "challenges", 
      "capacity", 
      "reaction", 
      "combat damage"
    ], 
    "name": "Metformin combats high glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells via inhibition of the NPR3-mediated MAPK pathway", 
    "pagination": "305", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1149508665"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/s13287-022-02992-z"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "35841070"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/s13287-022-02992-z", 
      "https://app.dimensions.ai/details/publication/pub.1149508665"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-11-24T21:09", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20221124/entities/gbq_results/article/article_943.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1186/s13287-022-02992-z"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s13287-022-02992-z'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s13287-022-02992-z'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s13287-022-02992-z'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s13287-022-02992-z'


 

This table displays all metadata directly associated to this object as RDF triples.

289 TRIPLES      21 PREDICATES      126 URIs      109 LITERALS      19 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s13287-022-02992-z schema:about N03ae2889ebc1415b973d72067f44f778
2 N1fbe3c7a42554b22912c57e603e18058
3 N67b028030b3745159c2fe7084dd637ee
4 N857888173dab4220b0b4c11e9b02222f
5 N88d1dd7cf98347b5b6772ef938cb2215
6 Na9c44359c8f044578eda085626ebeec0
7 Nb32506ec7feb49839424c2f8806ad091
8 Nd301db9357a04a20883a78fae475256d
9 Nd4b7fde433284650b4dd1c88d53b1f31
10 Nd6d7eef1b5f9492f80b5090389a59824
11 Ne5051d1845bd46b98a1ee505bd50729f
12 Nfdddac9688354a638c371e44a40bb0cf
13 anzsrc-for:06
14 anzsrc-for:0601
15 schema:author N52506fd203ef4ed59a1c158a57233439
16 schema:citation sg:pub.10.1007/s00018-012-0983-8
17 sg:pub.10.1007/s12015-018-9869-y
18 sg:pub.10.1038/nrendo.2011.106
19 sg:pub.10.1038/nri2395
20 sg:pub.10.1038/s41418-020-0593-1
21 sg:pub.10.1038/s41574-019-0242-2
22 sg:pub.10.1186/ar4253
23 sg:pub.10.1186/s13287-021-02322-9
24 sg:pub.10.1186/s13287-021-02618-w
25 schema:datePublished 2022-07-15
26 schema:datePublishedReg 2022-07-15
27 schema:description BackgroundHigh glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) has long been a challenge to periodontal regeneration for diabetic individuals. Metformin is an anti-hyperglycemic drug that exhibits abundant biological activities associated with cell metabolism and downstream tissue regeneration. However, how metformin combats damage to PDLSC osteogenic differentiation under high glucose and the underlying mechanisms remain unknown.MethodsOsteogenic differentiation of PDLSCs was assessed by alkaline phosphatase (ALP) staining, ALP activity, Alizarin Red staining and quantitative assay, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. RNA-seq analysis was performed to screen target genes of metformin, and the effects of target genes were confirmed using lentivirus transfection. Western blot analysis was also used to detect the protein level of underlying signaling pathways.ResultsWe found that osteogenic differentiation of PDLSCs under high glucose was decreased, and metformin addition enhanced this capacity of differentiation. Furthermore, the results of RNA-seq analysis showed that natriuretic peptide receptor 3 (NPR3) was upregulated in PDLSCs under high glucose and downregulated after metformin addition. When the underlying pathways involved were investigated, we found that upregulation of NPR3 can compromise the metformin-enhanced PDLSC osteogenic differentiation and activate the MAPK pathway (especially the p38 MAPK and Erk1/2 pathway), and that inhibition of the NPR3-mediated p38 MAPK or Erk1/2 pathway enhanced the osteogenic differentiation of PDLSCs under high glucose.ConclusionsThe present study suggests that metformin may enhance the osteogenic differentiation of PDLSCs under high glucose via downregulation of NPR3 and inhibition of its downstream MAPK pathway. This is the first report identifying the involvement of NPR3-mediated MAPK pathway in the metformin-enhanced osteogenic differentiation, indicating that NPR3 antagonists, such as metformin, may be feasible therapeutics for periodontal tissue regeneration in diabetic individuals.
28 schema:genre article
29 schema:isAccessibleForFree true
30 schema:isPartOf N541ff92a7ccf4b2e959c7c0558056555
31 N932dfb58644f40cf87afda6ab3e41b9f
32 sg:journal.1043222
33 schema:keywords ALP activity
34 ConclusionsThe present study
35 ERK1/2 pathway
36 MAPK
37 MAPK pathway
38 PDLSC osteogenic differentiation
39 RNA-seq analysis
40 ResultsWe
41 Western blot analysis
42 abundant biological activities
43 activity
44 addition
45 alizarin red staining
46 alkaline phosphatase staining
47 analysis
48 antagonist
49 anti-hyperglycemic drugs
50 biological activity
51 blot analysis
52 capacity
53 capacity of differentiation
54 cell metabolism
55 cells
56 chain reaction
57 challenges
58 combat damage
59 damage
60 diabetic individuals
61 differentiation
62 downregulation
63 downstream MAPK pathway
64 drugs
65 effect
66 feasible therapeutics
67 first report
68 genes
69 glucose
70 glucose-induced damage
71 high glucose
72 high glucose-induced damage
73 human periodontal ligament stem cells
74 individuals
75 inhibition
76 involvement
77 lentivirus transfection
78 levels
79 mechanism
80 metabolism
81 metformin
82 metformin addition
83 natriuretic peptide receptor 3
84 osteogenic differentiation
85 p38 MAPK
86 pathway
87 periodontal ligament stem cells
88 periodontal regeneration
89 periodontal tissue regeneration
90 phosphatase staining
91 polymerase chain reaction
92 present study
93 protein levels
94 quantitative real-time polymerase chain reaction
95 reaction
96 real-time polymerase chain reaction
97 receptor 3
98 red staining
99 regeneration
100 report
101 results
102 signaling pathways
103 staining
104 stem cells
105 study
106 target genes
107 therapeutics
108 tissue regeneration
109 transfection
110 underlying mechanism
111 underlying signaling pathways
112 upregulation
113 schema:name Metformin combats high glucose-induced damage to the osteogenic differentiation of human periodontal ligament stem cells via inhibition of the NPR3-mediated MAPK pathway
114 schema:pagination 305
115 schema:productId N0be1a56fa5424cc3bf4fb2e5ad3ae5ba
116 N46023c169da147d79eb9a1f8d2803197
117 N8044aec6e72c4b0ca88f8ede17369bd4
118 schema:sameAs https://app.dimensions.ai/details/publication/pub.1149508665
119 https://doi.org/10.1186/s13287-022-02992-z
120 schema:sdDatePublished 2022-11-24T21:09
121 schema:sdLicense https://scigraph.springernature.com/explorer/license/
122 schema:sdPublisher Ncb20cd46d7d6442bad71f28a9eb8a98c
123 schema:url https://doi.org/10.1186/s13287-022-02992-z
124 sgo:license sg:explorer/license/
125 sgo:sdDataset articles
126 rdf:type schema:ScholarlyArticle
127 N03ae2889ebc1415b973d72067f44f778 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
128 schema:name Periodontal Ligament
129 rdf:type schema:DefinedTerm
130 N0423d50d2a4a4586b5df3a3ff7e47302 rdf:first N0d82ebe45c83448ab690a61a3eadd2f6
131 rdf:rest Na24b12bdfde34f029c6074d6cc63596a
132 N0be1a56fa5424cc3bf4fb2e5ad3ae5ba schema:name pubmed_id
133 schema:value 35841070
134 rdf:type schema:PropertyValue
135 N0d82ebe45c83448ab690a61a3eadd2f6 schema:affiliation grid-institutes:grid.233520.5
136 schema:familyName Li
137 schema:givenName Zhi-Bang
138 rdf:type schema:Person
139 N1fbe3c7a42554b22912c57e603e18058 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
140 schema:name Receptors, Atrial Natriuretic Factor
141 rdf:type schema:DefinedTerm
142 N20a7676a86084e0aabff2fc7177813f1 rdf:first sg:person.0623606063.33
143 rdf:rest N5be04b75a7c94701a11720f3cf43f448
144 N46023c169da147d79eb9a1f8d2803197 schema:name doi
145 schema:value 10.1186/s13287-022-02992-z
146 rdf:type schema:PropertyValue
147 N4e9d301d2e844dd688f45b36f489065a rdf:first sg:person.016436034605.27
148 rdf:rest rdf:nil
149 N52506fd203ef4ed59a1c158a57233439 rdf:first Nebd27e05148a4e13b840dce9aea95a82
150 rdf:rest Nf5f404ca6a93457b80ba126f72e59b28
151 N541ff92a7ccf4b2e959c7c0558056555 schema:issueNumber 1
152 rdf:type schema:PublicationIssue
153 N5be04b75a7c94701a11720f3cf43f448 rdf:first sg:person.014455403635.21
154 rdf:rest Nc1054c5eeb5e4eddbc2c155c09afcad8
155 N67b028030b3745159c2fe7084dd637ee schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
156 schema:name p38 Mitogen-Activated Protein Kinases
157 rdf:type schema:DefinedTerm
158 N8044aec6e72c4b0ca88f8ede17369bd4 schema:name dimensions_id
159 schema:value pub.1149508665
160 rdf:type schema:PropertyValue
161 N857888173dab4220b0b4c11e9b02222f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
162 schema:name Osteogenesis
163 rdf:type schema:DefinedTerm
164 N88d1dd7cf98347b5b6772ef938cb2215 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
165 schema:name Glucose
166 rdf:type schema:DefinedTerm
167 N932dfb58644f40cf87afda6ab3e41b9f schema:volumeNumber 13
168 rdf:type schema:PublicationVolume
169 Na24b12bdfde34f029c6074d6cc63596a rdf:first sg:person.016264044545.43
170 rdf:rest Nbf12f5f3f6a0421ea456053aa2260bc4
171 Na9c44359c8f044578eda085626ebeec0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
172 schema:name Stem Cells
173 rdf:type schema:DefinedTerm
174 Nb0b4aa2b6723414eb1b03e3cb2408f0b rdf:first sg:person.0674130045.27
175 rdf:rest N20a7676a86084e0aabff2fc7177813f1
176 Nb32506ec7feb49839424c2f8806ad091 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
177 schema:name Cell Differentiation
178 rdf:type schema:DefinedTerm
179 Nbf12f5f3f6a0421ea456053aa2260bc4 rdf:first Nda0d6947204b4c37b08981084e682b34
180 rdf:rest Nb0b4aa2b6723414eb1b03e3cb2408f0b
181 Nc1054c5eeb5e4eddbc2c155c09afcad8 rdf:first sg:person.0651505472.53
182 rdf:rest N4e9d301d2e844dd688f45b36f489065a
183 Ncb20cd46d7d6442bad71f28a9eb8a98c schema:name Springer Nature - SN SciGraph project
184 rdf:type schema:Organization
185 Nd301db9357a04a20883a78fae475256d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
186 schema:name Cell Proliferation
187 rdf:type schema:DefinedTerm
188 Nd4b7fde433284650b4dd1c88d53b1f31 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
189 schema:name Humans
190 rdf:type schema:DefinedTerm
191 Nd6d7eef1b5f9492f80b5090389a59824 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
192 schema:name Metformin
193 rdf:type schema:DefinedTerm
194 Nda0d6947204b4c37b08981084e682b34 schema:affiliation grid-institutes:grid.233520.5
195 schema:familyName Li
196 schema:givenName Xuan
197 rdf:type schema:Person
198 Ne5051d1845bd46b98a1ee505bd50729f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
199 schema:name Cells, Cultured
200 rdf:type schema:DefinedTerm
201 Nebd27e05148a4e13b840dce9aea95a82 schema:affiliation grid-institutes:grid.233520.5
202 schema:familyName Zhang
203 schema:givenName Yi-Lin
204 rdf:type schema:Person
205 Nf5f404ca6a93457b80ba126f72e59b28 rdf:first Nfc76b508103344119efd8100c62383a6
206 rdf:rest N0423d50d2a4a4586b5df3a3ff7e47302
207 Nfc76b508103344119efd8100c62383a6 schema:affiliation grid-institutes:grid.440257.0
208 schema:familyName Liu
209 schema:givenName Fen
210 rdf:type schema:Person
211 Nfdddac9688354a638c371e44a40bb0cf schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
212 schema:name MAP Kinase Signaling System
213 rdf:type schema:DefinedTerm
214 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
215 schema:name Biological Sciences
216 rdf:type schema:DefinedTerm
217 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
218 schema:name Biochemistry and Cell Biology
219 rdf:type schema:DefinedTerm
220 sg:journal.1043222 schema:issn 1757-6512
221 schema:name Stem Cell Research & Therapy
222 schema:publisher Springer Nature
223 rdf:type schema:Periodical
224 sg:person.014455403635.21 schema:affiliation grid-institutes:grid.27255.37
225 schema:familyName Ge
226 schema:givenName Shao-Hua
227 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014455403635.21
228 rdf:type schema:Person
229 sg:person.016264044545.43 schema:affiliation grid-institutes:grid.233520.5
230 schema:familyName He
231 schema:givenName Xiao-Tao
232 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016264044545.43
233 rdf:type schema:Person
234 sg:person.016436034605.27 schema:affiliation grid-institutes:grid.233520.5
235 schema:familyName An
236 schema:givenName Ying
237 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016436034605.27
238 rdf:type schema:Person
239 sg:person.0623606063.33 schema:affiliation grid-institutes:grid.233520.5
240 schema:familyName Sun
241 schema:givenName Hai-Hua
242 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0623606063.33
243 rdf:type schema:Person
244 sg:person.0651505472.53 schema:affiliation grid-institutes:grid.233520.5
245 schema:familyName Chen
246 schema:givenName Fa-Ming
247 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0651505472.53
248 rdf:type schema:Person
249 sg:person.0674130045.27 schema:affiliation grid-institutes:grid.233520.5
250 schema:familyName Wu
251 schema:givenName Rui-Xin
252 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0674130045.27
253 rdf:type schema:Person
254 sg:pub.10.1007/s00018-012-0983-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051360008
255 https://doi.org/10.1007/s00018-012-0983-8
256 rdf:type schema:CreativeWork
257 sg:pub.10.1007/s12015-018-9869-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1111651697
258 https://doi.org/10.1007/s12015-018-9869-y
259 rdf:type schema:CreativeWork
260 sg:pub.10.1038/nrendo.2011.106 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034661192
261 https://doi.org/10.1038/nrendo.2011.106
262 rdf:type schema:CreativeWork
263 sg:pub.10.1038/nri2395 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034703692
264 https://doi.org/10.1038/nri2395
265 rdf:type schema:CreativeWork
266 sg:pub.10.1038/s41418-020-0593-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1129565834
267 https://doi.org/10.1038/s41418-020-0593-1
268 rdf:type schema:CreativeWork
269 sg:pub.10.1038/s41574-019-0242-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1120494863
270 https://doi.org/10.1038/s41574-019-0242-2
271 rdf:type schema:CreativeWork
272 sg:pub.10.1186/ar4253 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042771043
273 https://doi.org/10.1186/ar4253
274 rdf:type schema:CreativeWork
275 sg:pub.10.1186/s13287-021-02322-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1137601306
276 https://doi.org/10.1186/s13287-021-02322-9
277 rdf:type schema:CreativeWork
278 sg:pub.10.1186/s13287-021-02618-w schema:sameAs https://app.dimensions.ai/details/publication/pub.1141971507
279 https://doi.org/10.1186/s13287-021-02618-w
280 rdf:type schema:CreativeWork
281 grid-institutes:grid.233520.5 schema:alternateName State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi’an, People’s Republic of China
282 schema:name State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, Fourth Military Medical University, 710032, Xi’an, People’s Republic of China
283 rdf:type schema:Organization
284 grid-institutes:grid.27255.37 schema:alternateName Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China
285 schema:name Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China
286 rdf:type schema:Organization
287 grid-institutes:grid.440257.0 schema:alternateName Department of Stomatology Northwest Women’s and Children’s Hospital, Xi’an, Shaanxi, People’s Republic of China
288 schema:name Department of Stomatology Northwest Women’s and Children’s Hospital, Xi’an, Shaanxi, People’s Republic of China
289 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...