CCR3 antagonist protects against induced cellular senescence and promotes rejuvenation in periodontal ligament cells for stimulating pulp regeneration in the aged dog

Sci Rep. 2020 May 25;10(1):8631. doi: 10.1038/s41598-020-65301-9.

Abstract

Pulp regeneration after transplantation of mobilized dental pulp stem cells (MDPSCs) declines in the aged dogs due in part to the chronic inflammation and/or cellular senescence. Eotaxin-1/C-C motif chemokine 11 (CCL11) is an inflammation marker via chemokine receptor 3 (CCR3). Moreover, CCR3 antagonist (CCR3A) can inhibit CCL11 binding to CCR3 and prevent CCL11/CCR3 signaling. The study aimed to examine the effect of CCR3A on cellular senescence and anti-inflammation/immunomodulation in human periodontal ligament cells (HPDLCs). The rejuvenating effects of CCR3A on neurite extension and migratory activity to promote pulp regeneration in aged dog teeth were also evaluated. In vivo, the amount of regenerated pulp tissues was significantly increased by transplantation of MDPSCs with CCR3A compared to control without CCR3A. In vitro, senescence of HPDLCs was induced after p-Cresol exposure, as indicated by increased cell size, decreased proliferation and increased senescence markers, p21 and IL-1β. Treatment of HPDLCs with CCR3A prevented the senescence effect of p-Cresol. Furthermore, CCR3A significantly decreased expression of CCL11, increased expression of immunomodulatory factor, IDO, and enhanced neurite extension and migratory activity. In conclusion, CCR3A protects against p-Cresol-induced cellular senescence and enhances rejuvenating effects, suggesting its potential utility to stimulate pulp regeneration in the aged teeth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cellular Senescence* / drug effects
  • Chemokine CCL11 / metabolism
  • Cresols / pharmacology
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Dental Pulp / cytology
  • Dental Pulp / physiology*
  • Dogs
  • Humans
  • Interleukin-1beta / metabolism
  • Neurites / physiology
  • Periodontal Ligament / cytology
  • Periodontal Ligament / metabolism
  • Receptors, CCR3 / antagonists & inhibitors*
  • Receptors, CCR3 / metabolism
  • Regeneration / drug effects
  • Rejuvenation*
  • Stem Cell Transplantation
  • Stem Cells / cytology
  • Stem Cells / metabolism

Substances

  • Chemokine CCL11
  • Cresols
  • Cyclin-Dependent Kinase Inhibitor p21
  • Interleukin-1beta
  • Receptors, CCR3
  • 4-cresol