Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance the Osteoblastic Differentiation of Periodontal Ligament Stem Cells Under High Glucose Conditions Through the PI3K/AKT Signaling Pathway

Biomed Environ Sci. 2022 Sep 20;35(9):811-820. doi: 10.3967/bes2022.105.

Abstract

Objective: High glucose (HG) can influence the osteogenic differentiation ability of periodontal ligament stem cells (PDLSCs). Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-exo) have broad application prospects in tissue healing. The current study aimed to explore whether hUCMSC-exo could promote the osteogenic differentiation of hPDLSCs under HG conditions and the underlying mechanism.

Methods: We used a 30 mmol/L glucose concentration to simulate HG conditions. CCK-8 assay was performed to evaluate the effect of hUCMSC-exo on the proliferation of hPDLSCs. Alkaline phosphatase (ALP) staining, ALP activity, and qRT-PCR were performed to evaluate the pro-osteogenic effect of hUCMSC-exo on hPDLSCs. Western blot analysis was conducted to evaluate the underlying mechanism.

Results: The results of the CCK-8 assay, ALP staining, ALP activity, and qRT-PCR assay showed that hUCMSC-exo significantly promoted cell proliferation and osteogenic differentiation in a dose-dependent manner. The Western blot results revealed that hUCMSC-exo significantly increased the levels of p-PI3K and p-AKT in cells, and the effect was inhibited by LY294002 (PI3K inhibitor) or MK2206 (AKT inhibitor), respectively. Moreover, the increases in osteogenic indicators induced by hUCMSC-exo were significantly suppressed by LY294002 and MK2206.

Conclusion: hUCMSC-exo promote the osteogenic differentiation of hPDLSCs under HG conditions through the PI3K/AKT signaling pathway.

Keywords: Exosomes; High glucose; Human umbilical cord mesenchymal stem cell; Osteogenic differentiation; PI3K/AKT; Periodontal ligament stem cell.

MeSH terms

  • Alkaline Phosphatase
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Exosomes* / metabolism
  • Glucose / metabolism
  • Glucose / pharmacology
  • Humans
  • Mesenchymal Stem Cells* / metabolism
  • Osteogenesis
  • Periodontal Ligament / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Stem Cells / metabolism
  • Umbilical Cord / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Alkaline Phosphatase
  • Glucose