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", 
        "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", 
        "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.10.1186/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/nri2395", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034703692", 
          "https://doi.org/10.1038/nri2395"
        ], 
        "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/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.10.1038/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.10.1007/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/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/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/s41418-020-0593-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1129565834", 
          "https://doi.org/10.1038/s41418-020-0593-1"
        ], 
        "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": "2022-09-02T16:07", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220902/entities/gbq_results/article/article_925.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.

287 TRIPLES      21 PREDICATES      126 URIs      109 LITERALS      19 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s13287-022-02992-z schema:about N12d451ed6cb142eb88ff30adacd53a0f
2 N130391e3d20e428f9827e27036a7c423
3 N2f9b2ff6286d40cb9d914238644ed754
4 N53ff91967d0a428d95cca92c563b233d
5 N5b5dad5099d24dfaa15f175610ff874c
6 N69440bd4f49944f492ea043652cdeafc
7 N7b5688f5807a4a2285141de0e97ef5bd
8 N8afe7fbda38f4a20ae7cddb97739dc28
9 N902f8da5d029435e8607b6ce4ed22cc1
10 Nab5397ee4c0e4714a83c54633db7efda
11 Nb035472769074386ad0c62a9414e3b5e
12 Nedf5547d65394e55843cf8b0dd47d587
13 anzsrc-for:06
14 anzsrc-for:0601
15 schema:author N4204b9ae6079409e95d250c8364257b0
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 N117504c9975b474eb3ede4c3555e434f
31 Na5357fc97f3e4ed7916202f7e667ccea
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 N12d6b9ad6b104433ad8504903c1696ff
116 N4c96579e18b04e048d75e1ba80b02b6c
117 N9f163729976e478d82b857d6c583d60b
118 schema:sameAs https://app.dimensions.ai/details/publication/pub.1149508665
119 https://doi.org/10.1186/s13287-022-02992-z
120 schema:sdDatePublished 2022-09-02T16:07
121 schema:sdLicense https://scigraph.springernature.com/explorer/license/
122 schema:sdPublisher N29f5535205f04322b388593464df1f15
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 N10ad6f4563f7448b8cf48cb6de5d78c0 rdf:first N86ef90eb69e74997bc7088171ff60a2e
128 rdf:rest Nd4bad542c4904267afc63205221e4401
129 N117504c9975b474eb3ede4c3555e434f schema:issueNumber 1
130 rdf:type schema:PublicationIssue
131 N12d451ed6cb142eb88ff30adacd53a0f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
132 schema:name Cells, Cultured
133 rdf:type schema:DefinedTerm
134 N12d6b9ad6b104433ad8504903c1696ff schema:name dimensions_id
135 schema:value pub.1149508665
136 rdf:type schema:PropertyValue
137 N130391e3d20e428f9827e27036a7c423 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
138 schema:name Cell Differentiation
139 rdf:type schema:DefinedTerm
140 N182dfcf6f69240b089a7c88d51397a7b schema:affiliation grid-institutes:grid.233520.5
141 schema:familyName Li
142 schema:givenName Zhi-Bang
143 rdf:type schema:Person
144 N29f5535205f04322b388593464df1f15 schema:name Springer Nature - SN SciGraph project
145 rdf:type schema:Organization
146 N2f9b2ff6286d40cb9d914238644ed754 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
147 schema:name p38 Mitogen-Activated Protein Kinases
148 rdf:type schema:DefinedTerm
149 N3a3939ab097f42c3b99bccb0a49c9d51 schema:affiliation grid-institutes:grid.233520.5
150 schema:familyName Zhang
151 schema:givenName Yi-Lin
152 rdf:type schema:Person
153 N3f566fe3fa0f412ab0095661069795c1 rdf:first N78e92b6aecb54ffaa1205fc2e0f15628
154 rdf:rest N89a2751c5d6c47f6ab803d27162b9157
155 N4204b9ae6079409e95d250c8364257b0 rdf:first N3a3939ab097f42c3b99bccb0a49c9d51
156 rdf:rest Nccb7cf8efc7d480da1660afbbab8222e
157 N4c96579e18b04e048d75e1ba80b02b6c schema:name doi
158 schema:value 10.1186/s13287-022-02992-z
159 rdf:type schema:PropertyValue
160 N53ff91967d0a428d95cca92c563b233d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
161 schema:name Stem Cells
162 rdf:type schema:DefinedTerm
163 N5ac2ac7446404f4cb8dfb03dcf9b1957 schema:affiliation grid-institutes:grid.233520.5
164 schema:familyName He
165 schema:givenName Xiao-Tao
166 rdf:type schema:Person
167 N5b5dad5099d24dfaa15f175610ff874c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
168 schema:name Metformin
169 rdf:type schema:DefinedTerm
170 N69440bd4f49944f492ea043652cdeafc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
171 schema:name Receptors, Atrial Natriuretic Factor
172 rdf:type schema:DefinedTerm
173 N779e3b37fb7d4f368dcbff5e06e50a18 rdf:first N5ac2ac7446404f4cb8dfb03dcf9b1957
174 rdf:rest N10ad6f4563f7448b8cf48cb6de5d78c0
175 N78e92b6aecb54ffaa1205fc2e0f15628 schema:affiliation grid-institutes:grid.233520.5
176 schema:familyName Sun
177 schema:givenName Hai-Hua
178 rdf:type schema:Person
179 N7b5688f5807a4a2285141de0e97ef5bd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
180 schema:name MAP Kinase Signaling System
181 rdf:type schema:DefinedTerm
182 N86ef90eb69e74997bc7088171ff60a2e schema:affiliation grid-institutes:grid.233520.5
183 schema:familyName Li
184 schema:givenName Xuan
185 rdf:type schema:Person
186 N89a2751c5d6c47f6ab803d27162b9157 rdf:first sg:person.014455403635.21
187 rdf:rest Nfc37014c4a3a4ca5ba646d247c4e3778
188 N8afe7fbda38f4a20ae7cddb97739dc28 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
189 schema:name Periodontal Ligament
190 rdf:type schema:DefinedTerm
191 N902f8da5d029435e8607b6ce4ed22cc1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
192 schema:name Osteogenesis
193 rdf:type schema:DefinedTerm
194 N9f163729976e478d82b857d6c583d60b schema:name pubmed_id
195 schema:value 35841070
196 rdf:type schema:PropertyValue
197 Na5357fc97f3e4ed7916202f7e667ccea schema:volumeNumber 13
198 rdf:type schema:PublicationVolume
199 Nab5397ee4c0e4714a83c54633db7efda schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
200 schema:name Glucose
201 rdf:type schema:DefinedTerm
202 Nb035472769074386ad0c62a9414e3b5e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
203 schema:name Humans
204 rdf:type schema:DefinedTerm
205 Nc3600b5e5ebf466485388cd0ba0c1643 schema:affiliation grid-institutes:grid.440257.0
206 schema:familyName Liu
207 schema:givenName Fen
208 rdf:type schema:Person
209 Nccb7cf8efc7d480da1660afbbab8222e rdf:first Nc3600b5e5ebf466485388cd0ba0c1643
210 rdf:rest Ne62a131db9d5454cb3be48fe113e211c
211 Nd4bad542c4904267afc63205221e4401 rdf:first sg:person.0674130045.27
212 rdf:rest N3f566fe3fa0f412ab0095661069795c1
213 Nd53aba12c6584868870f7e07b334a7c2 rdf:first sg:person.016436034605.27
214 rdf:rest rdf:nil
215 Ne62a131db9d5454cb3be48fe113e211c rdf:first N182dfcf6f69240b089a7c88d51397a7b
216 rdf:rest N779e3b37fb7d4f368dcbff5e06e50a18
217 Nedf5547d65394e55843cf8b0dd47d587 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
218 schema:name Cell Proliferation
219 rdf:type schema:DefinedTerm
220 Nfc37014c4a3a4ca5ba646d247c4e3778 rdf:first sg:person.0651505472.53
221 rdf:rest Nd53aba12c6584868870f7e07b334a7c2
222 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
223 schema:name Biological Sciences
224 rdf:type schema:DefinedTerm
225 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
226 schema:name Biochemistry and Cell Biology
227 rdf:type schema:DefinedTerm
228 sg:journal.1043222 schema:issn 1757-6512
229 schema:name Stem Cell Research & Therapy
230 schema:publisher Springer Nature
231 rdf:type schema:Periodical
232 sg:person.014455403635.21 schema:affiliation grid-institutes:grid.27255.37
233 schema:familyName Ge
234 schema:givenName Shao-Hua
235 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014455403635.21
236 rdf:type schema:Person
237 sg:person.016436034605.27 schema:affiliation grid-institutes:grid.233520.5
238 schema:familyName An
239 schema:givenName Ying
240 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016436034605.27
241 rdf:type schema:Person
242 sg:person.0651505472.53 schema:affiliation grid-institutes:grid.233520.5
243 schema:familyName Chen
244 schema:givenName Fa-Ming
245 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0651505472.53
246 rdf:type schema:Person
247 sg:person.0674130045.27 schema:affiliation grid-institutes:grid.233520.5
248 schema:familyName Wu
249 schema:givenName Rui-Xin
250 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0674130045.27
251 rdf:type schema:Person
252 sg:pub.10.1007/s00018-012-0983-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051360008
253 https://doi.org/10.1007/s00018-012-0983-8
254 rdf:type schema:CreativeWork
255 sg:pub.10.1007/s12015-018-9869-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1111651697
256 https://doi.org/10.1007/s12015-018-9869-y
257 rdf:type schema:CreativeWork
258 sg:pub.10.1038/nrendo.2011.106 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034661192
259 https://doi.org/10.1038/nrendo.2011.106
260 rdf:type schema:CreativeWork
261 sg:pub.10.1038/nri2395 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034703692
262 https://doi.org/10.1038/nri2395
263 rdf:type schema:CreativeWork
264 sg:pub.10.1038/s41418-020-0593-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1129565834
265 https://doi.org/10.1038/s41418-020-0593-1
266 rdf:type schema:CreativeWork
267 sg:pub.10.1038/s41574-019-0242-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1120494863
268 https://doi.org/10.1038/s41574-019-0242-2
269 rdf:type schema:CreativeWork
270 sg:pub.10.1186/ar4253 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042771043
271 https://doi.org/10.1186/ar4253
272 rdf:type schema:CreativeWork
273 sg:pub.10.1186/s13287-021-02322-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1137601306
274 https://doi.org/10.1186/s13287-021-02322-9
275 rdf:type schema:CreativeWork
276 sg:pub.10.1186/s13287-021-02618-w schema:sameAs https://app.dimensions.ai/details/publication/pub.1141971507
277 https://doi.org/10.1186/s13287-021-02618-w
278 rdf:type schema:CreativeWork
279 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
280 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
281 rdf:type schema:Organization
282 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
283 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
284 rdf:type schema:Organization
285 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
286 schema:name Department of Stomatology Northwest Women’s and Children’s Hospital, Xi’an, Shaanxi, People’s Republic of China
287 rdf:type schema:Organization
 




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


...