PDGF-AA guides cell crosstalk between human dental pulp stem cells in vitro via the PDGFR-α/PI3K/Akt axis

Int Endod J. 2024 May;57(5):549-565. doi: 10.1111/iej.14038. Epub 2024 Feb 9.

Abstract

Aim: To explore the influence of PDGF-AA on cell communication between human dental pulp stem cells (DPSCs) by characterizing gap junction intercellular communication (GJIC) and its potential biomechanical mechanism.

Methodology: Quantitative real-time PCR was used to measure connexin family member expression in DPSCs. Cell migration and CCK-8 assays were utilized to examine the influence of PDGF-AA on DPSC migration and proliferation. A scrape loading/dye transfer assay was applied to evaluate GJIC triggered by PDGF-AA, a PI3K/Akt signalling pathway blocker (LY294002) and a PDGFR-α blocker (AG1296). Western blotting and immunofluorescence were used to test the expression and distribution of the Cx43 and p-Akt proteins in DPSCs. Scanning electron microscopy (SEM) and immunofluorescence were used to observe the morphology of GJIC in DPSCs.

Results: PDGF-AA promoted gap junction formation and intercellular communication between human dental pulp stem cells. PDGF-AA upregulates the expression of Cx43 to enhance gap junction formation and intercellular communication. PDGF-AA binds to PDGFR-α and activates PI3K/Akt signalling to regulate cell communication.

Conclusions: This research demonstrated that PDGF-AA can enhance Cx43-mediated GJIC in DPSCs via the PDGFR-α/PI3K/Akt axis, which provides new cues for dental pulp regeneration from the perspective of intercellular communication.

Keywords: connexin 43; dental pulp stem cells; gap junction intercellular communication; platelet‐derived growth factor AA.

MeSH terms

  • Connexin 43 / metabolism
  • Dental Pulp*
  • Humans
  • Phosphatidylinositol 3-Kinases
  • Platelet-Derived Growth Factor*
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Receptor, Platelet-Derived Growth Factor alpha
  • Regeneration
  • Stem Cells / metabolism

Substances

  • platelet-derived growth factor A
  • Proto-Oncogene Proteins c-akt
  • Connexin 43
  • Phosphatidylinositol 3-Kinases
  • Receptor, Platelet-Derived Growth Factor alpha
  • Platelet-Derived Growth Factor