PDLSCs Regulate Angiogenesis of Periodontal Ligaments via VEGF Transferred by Exosomes in Periodontitis

Int J Med Sci. 2020 Feb 10;17(5):558-567. doi: 10.7150/ijms.40918. eCollection 2020.

Abstract

Abnormal angiogenesis is one of the significant features in periodontitis leading to progressive inflammation, but angiogenic changes of periodontal ligaments under inflammatory condition were rarely reported. Periodontal ligament stem cells (PDLSCs) were a kind of dental stem cells associated with vascularization. Here we investigated the alteration of angiogenesis of periodontal ligament in periodontitis, and revealed an exosome-mediated pathway to support the effect of PDLSCs on angiogenic improvement. Vascular specific marker CD31 and VEGFA were found to be highly expressed in periodontal ligaments of periodontitis. The VEGFA expression was up-regulated in inflamed PDLSCs compared to control, meanwhile the tube formation of HUVECs was improved when co-cultured with inflamed PDLSCs. Exosomes secretion of PDSLCs was augmented by inflammation, and promoted angiogenesis of HUVECs, whereas blocking secretion of exosomes led to degenerated angiogenesis of HUVECs. Exosome-trasferred VEGFA was proven to be the crucial communicator between PDLSCs and HUVECs. Inflammation inhibited miR-17-5p expression of PDLSCs and relieved its target VEGFA. However, overexpression of miR-17-5p blocked the pro-angiogenic ability of inflamed PDLSCs. In conclusion, the findings indicated that vascularization of periodontal ligaments was enhanced, and inflammatory micro-environment of periodontitis facilitated pro-angiogenesis of PDLSCs through regulating exosome-mediated transfer of VEGFA, which was targeted by miR-17-5p.

Keywords: PDLSCs; VEGF; angiogenesis; exosomes; miR-17-5p; periodontitis.

MeSH terms

  • Animals
  • Chronic Periodontitis / physiopathology*
  • Exosomes / physiology
  • Female
  • Gingiva / blood supply
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • MicroRNAs / metabolism*
  • Neovascularization, Pathologic*
  • Periodontal Ligament / blood supply*
  • Periodontal Ligament / cytology
  • Rats, Sprague-Dawley
  • Stem Cells / physiology
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • MIRN17 microRNA, human
  • MicroRNAs
  • Vascular Endothelial Growth Factor A