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Protein Arginine Methyltransferase 6 Regulated Odontogenic Differentiation and Mitochondrial Function of Stem Cells from Apical Papilla Through its Nuclear Localization Sequence via β-catenin Pathway.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Protein Arginine Methyltransferase 6 Regulated Odontogenic Differentiation and Mitochondrial Function of Stem Cells from Apical Papilla Through its Nuclear Localization Sequence via β-catenin Pathway.
Συγγραφείς: Yan W; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China; Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China., Guo X; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China; Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China., Zhao B; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China., Li Y; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China., Shen Z; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China., Shi R; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China. Electronic address: shiruitang@126.com., Zhang C; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China. Electronic address: zhangchen710cool@qq.com.
Πηγή: International dental journal [Int Dent J] 2026 Aug; Vol. 76 (4), pp. 109680. Date of Electronic Publication: 2026 Jun 13.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Country of Publication: England NLM ID: 0374714 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1875-595X (Electronic) Linking ISSN: 00206539 NLM ISO Abbreviation: Int Dent J Subsets: MEDLINE
Imprint Name(s): Publication: 2021- : London : Elsevier
Original Publication: London : FDI World Dental
Ιατρικοί όροι (MeSH): Protein-Arginine N-Methyltransferases*/metabolism , Protein-Arginine N-Methyltransferases*/physiology , beta Catenin*/metabolism , Cell Differentiation*/physiology , Mitochondria*/physiology , Mitochondria*/metabolism , Stem Cells*/physiology , Stem Cells*/cytology , Odontogenesis*/physiology , Dental Papilla*/cytology , Nuclear Localization Signals*, Osteogenesis/physiology ; Animals ; Mice ; Humans ; Mice, Nude ; Cells, Cultured ; Flow Cytometry ; Signal Transduction ; Microscopy, Electron, Transmission ; Blotting, Western
Περίληψη: Objectives: Odontogenic differentiation of stem cells from apical papilla (SCAPs) is critical for pulp regeneration therapy. Protein arginine methyltransferase 6 (PRMT6) plays an important role in stem cell differentiation, but the specific functions and mechanisms remain unclear. This study aimed to explore the role of PRMT6 nuclear localization sequence (NLS) in regulating SCAPs osteogenic and odontogenic differentiation and its underlying mechanism.
Materials and Methods: SCAPs were isolated and identified by flow cytometry. Wild-type PRMT6 and NLS-deleted PRMT6 (PRMT6ΔNLS) overexpression models were constructed via lentiviral infection. Osteogenic and odontogenic differentiation was evaluated via alkaline phosphatase staining, Alizarin Red staining, western blot, and in vivo nude mouse transplantation. Mitochondrial function was analysed by transmission electron microscopy, mitochondrial stress testing, and JC-10 membrane potential assays. Downstream gene expression and β-catenin pathway activity were examined via real-time RT-PCR, western blot, and rescue experiments were performed by exogenous Dickkopf‑1 (DKK1) supplementation.
Results: PRMT6 exhibited nucleocytoplasmic redistribution during early odontogenic differentiation of SCAPs, with increased nuclear export. NLS mutation reduced PRMT6 nuclear accumulation, reversed PRMT6-mediated inhibition of in vitro mineralization and osteogenic and odontogenic marker expression, and promoted in vivo bone-/dentin-like tissue formation. Additionally, PRMT6ΔNLS rescued mitochondrial ultrastructural damage, increased OCR and mitochondrial membrane potential, and improved mitochondrial function. Mechanistically, PRMT6ΔNLS downregulated Wnt antagonist DKK1, activated the β-catenin pathway, and exogenous DKK1 abolished this pro-differentiation effect.
Conclusions: PRMT6 nuclear localization is essential for its inhibitory effect on SCAPs osteogenic and odontogenic differentiation. NLS-deleted PRMT6 promotes SCAPs differentiation by rescuing mitochondrial function and activating the β-catenin pathway via downregulating DKK1.
Clinical Significance: This study provides a theoretical basis and potential targets for promoting dentin-pulp regeneration by modulating PRMT6 nuclear transport.
(Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of competing interest None disclosed.
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Contributed Indexing: Keywords: Mitochondrial energy metabolism; Nuclear transport; Osteogenic and odontogenic differentiation; Protein arginine methyltransferase 6; Stem cells from apical papilla; β-catenin signalling pathway
Substance Nomenclature: EC 2.1.1.319 (Protein-Arginine N-Methyltransferases)
0 (beta Catenin)
0 (Nuclear Localization Signals)
Entry Date(s): Date Created: 20260613 Date Completed: 20260707 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC13279183
DOI: 10.1016/j.identj.2026.109680
PMID: 42288015
Βάση Δεδομένων: MEDLINE
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Items – Name: Title
  Label: Title
  Group: Ti
  Data: Protein Arginine Methyltransferase 6 Regulated Odontogenic Differentiation and Mitochondrial Function of Stem Cells from Apical Papilla Through its Nuclear Localization Sequence via β-catenin Pathway.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AU" term="%22Yan+W%22">Yan W</searchLink>; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China; Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.<br /><searchLink fieldCode="AU" term="%22Guo+X%22">Guo X</searchLink>; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China; Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.<br /><searchLink fieldCode="AU" term="%22Zhao+B%22">Zhao B</searchLink>; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.<br /><searchLink fieldCode="AU" term="%22Li+Y%22">Li Y</searchLink>; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.<br /><searchLink fieldCode="AU" term="%22Shen+Z%22">Shen Z</searchLink>; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.<br /><searchLink fieldCode="AU" term="%22Shi+R%22">Shi R</searchLink>; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China. Electronic address: shiruitang@126.com.<br /><searchLink fieldCode="AU" term="%22Zhang+C%22">Zhang C</searchLink>; Department of Endodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China. Electronic address: zhangchen710cool@qq.com.
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  Data: <searchLink fieldCode="JN" term="%220374714%22">International dental journal</searchLink> [Int Dent J] 2026 Aug; Vol. 76 (4), pp. 109680. <i>Date of Electronic Publication: </i>2026 Jun 13.
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  Data: Journal Article
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Elsevier%22">Elsevier </searchLink><i>Country of Publication: </i>England <i>NLM ID: </i>0374714 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1875-595X (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2200206539%22">00206539 </searchLink><i>NLM ISO Abbreviation: </i>Int Dent J <i>Subsets: </i>MEDLINE
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  Data: <i>Publication</i>: 2021- : London : Elsevier<br /><i>Original Publication</i>: London : FDI World Dental
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: <searchLink fieldCode="MM" term="%22Protein-Arginine+N-Methyltransferases%22">Protein-Arginine N-Methyltransferases*</searchLink>/<searchLink fieldCode="MM" term="%22Protein-Arginine+N-Methyltransferases+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Protein-Arginine+N-Methyltransferases%22">Protein-Arginine N-Methyltransferases*</searchLink>/<searchLink fieldCode="MM" term="%22Protein-Arginine+N-Methyltransferases+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22beta+Catenin%22">beta Catenin*</searchLink>/<searchLink fieldCode="MM" term="%22beta+Catenin+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Cell+Differentiation%22">Cell Differentiation*</searchLink>/<searchLink fieldCode="MM" term="%22Cell+Differentiation+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Mitochondria%22">Mitochondria*</searchLink>/<searchLink fieldCode="MM" term="%22Mitochondria+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Mitochondria%22">Mitochondria*</searchLink>/<searchLink fieldCode="MM" term="%22Mitochondria+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Stem+Cells%22">Stem Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Stem+Cells+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Stem+Cells%22">Stem Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Stem+Cells+cytology%22">cytology</searchLink> <br /><searchLink fieldCode="MM" term="%22Odontogenesis%22">Odontogenesis*</searchLink>/<searchLink fieldCode="MM" term="%22Odontogenesis+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Dental+Papilla%22">Dental Papilla*</searchLink>/<searchLink fieldCode="MM" term="%22Dental+Papilla+cytology%22">cytology</searchLink> <br /><searchLink fieldCode="MM" term="%22Nuclear+Localization+Signals%22">Nuclear Localization Signals*</searchLink><br /><searchLink fieldCode="MH" term="%22Osteogenesis%22">Osteogenesis</searchLink>/<searchLink fieldCode="MH" term="%22Osteogenesis+physiology%22">physiology</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%2C+Nude%22">Mice, Nude</searchLink> ; <searchLink fieldCode="MH" term="%22Cells%2C+Cultured%22">Cells, Cultured</searchLink> ; <searchLink fieldCode="MH" term="%22Flow+Cytometry%22">Flow Cytometry</searchLink> ; <searchLink fieldCode="MH" term="%22Signal+Transduction%22">Signal Transduction</searchLink> ; <searchLink fieldCode="MH" term="%22Microscopy%2C+Electron%2C+Transmission%22">Microscopy, Electron, Transmission</searchLink> ; <searchLink fieldCode="MH" term="%22Blotting%2C+Western%22">Blotting, Western</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Objectives: Odontogenic differentiation of stem cells from apical papilla (SCAPs) is critical for pulp regeneration therapy. Protein arginine methyltransferase 6 (PRMT6) plays an important role in stem cell differentiation, but the specific functions and mechanisms remain unclear. This study aimed to explore the role of PRMT6 nuclear localization sequence (NLS) in regulating SCAPs osteogenic and odontogenic differentiation and its underlying mechanism.<br />Materials and Methods: SCAPs were isolated and identified by flow cytometry. Wild-type PRMT6 and NLS-deleted PRMT6 (PRMT6ΔNLS) overexpression models were constructed via lentiviral infection. Osteogenic and odontogenic differentiation was evaluated via alkaline phosphatase staining, Alizarin Red staining, western blot, and in vivo nude mouse transplantation. Mitochondrial function was analysed by transmission electron microscopy, mitochondrial stress testing, and JC-10 membrane potential assays. Downstream gene expression and β-catenin pathway activity were examined via real-time RT-PCR, western blot, and rescue experiments were performed by exogenous Dickkopf‑1 (DKK1) supplementation.<br />Results: PRMT6 exhibited nucleocytoplasmic redistribution during early odontogenic differentiation of SCAPs, with increased nuclear export. NLS mutation reduced PRMT6 nuclear accumulation, reversed PRMT6-mediated inhibition of in vitro mineralization and osteogenic and odontogenic marker expression, and promoted in vivo bone-/dentin-like tissue formation. Additionally, PRMT6ΔNLS rescued mitochondrial ultrastructural damage, increased OCR and mitochondrial membrane potential, and improved mitochondrial function. Mechanistically, PRMT6ΔNLS downregulated Wnt antagonist DKK1, activated the β-catenin pathway, and exogenous DKK1 abolished this pro-differentiation effect.<br />Conclusions: PRMT6 nuclear localization is essential for its inhibitory effect on SCAPs osteogenic and odontogenic differentiation. NLS-deleted PRMT6 promotes SCAPs differentiation by rescuing mitochondrial function and activating the β-catenin pathway via downregulating DKK1.<br />Clinical Significance: This study provides a theoretical basis and potential targets for promoting dentin-pulp regeneration by modulating PRMT6 nuclear transport.<br /> (Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of competing interest None disclosed.
– Name: Ref
  Label: References
  Group: RefInfo
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– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>Mitochondrial energy metabolism; Nuclear transport; Osteogenic and odontogenic differentiation; Protein arginine methyltransferase 6; Stem cells from apical papilla; β-catenin signalling pathway
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: EC 2.1.1.319 (Protein-Arginine N-Methyltransferases)<br />0 (beta Catenin)<br />0 (Nuclear Localization Signals)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20260613 <i>Date Completed: </i>20260707 <i>Latest Revision: </i>20260813
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260813
– Name: PubmedCentralID
  Label: PubMed Central ID
  Group: ID
  Data: PMC13279183
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1016/j.identj.2026.109680
– Name: AN
  Label: PMID
  Group: ID
  Data: 42288015
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42288015
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/j.identj.2026.109680
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 109680
    Subjects:
      – SubjectFull: Osteogenesis physiology
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Mice, Nude
        Type: general
      – SubjectFull: Cells, Cultured
        Type: general
      – SubjectFull: Flow Cytometry
        Type: general
      – SubjectFull: Signal Transduction
        Type: general
      – SubjectFull: Microscopy, Electron, Transmission
        Type: general
      – SubjectFull: Blotting, Western
        Type: general
      – SubjectFull: Protein-Arginine N-Methyltransferases metabolism
        Type: general
      – SubjectFull: Protein-Arginine N-Methyltransferases physiology
        Type: general
      – SubjectFull: beta Catenin metabolism
        Type: general
      – SubjectFull: Cell Differentiation physiology
        Type: general
      – SubjectFull: Mitochondria physiology
        Type: general
      – SubjectFull: Mitochondria metabolism
        Type: general
      – SubjectFull: Stem Cells physiology
        Type: general
      – SubjectFull: Stem Cells cytology
        Type: general
      – SubjectFull: Odontogenesis physiology
        Type: general
      – SubjectFull: Dental Papilla cytology
        Type: general
      – SubjectFull: Nuclear Localization Signals
        Type: general
    Titles:
      – TitleFull: Protein Arginine Methyltransferase 6 Regulated Odontogenic Differentiation and Mitochondrial Function of Stem Cells from Apical Papilla Through its Nuclear Localization Sequence via β-catenin Pathway.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Yan W
      – PersonEntity:
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            NameFull: Guo X
      – PersonEntity:
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            NameFull: Zhao B
      – PersonEntity:
          Name:
            NameFull: Li Y
      – PersonEntity:
          Name:
            NameFull: Shen Z
      – PersonEntity:
          Name:
            NameFull: Shi R
      – PersonEntity:
          Name:
            NameFull: Zhang C
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 08
              Text: 2026 Aug
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1875-595X
          Numbering:
            – Type: volume
              Value: 76
            – Type: issue
              Value: 4
          Titles:
            – TitleFull: International dental journal
              Type: main
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