Betamethasone suppresses the inflammatory response in LPS-stimulated dental pulp cells through inhibition of NF-κB

Arch Oral Biol. 2019 Feb:98:156-163. doi: 10.1016/j.archoralbio.2018.11.022. Epub 2018 Nov 20.

Abstract

Objective: This study aimed to investigate the anti-inflammatory effect of betamethasone on LPS-stimulated human dental pulp stem cells (DPSCs) and its associated mechanism. The osteo-/odontogenic differentiation and osteoclast effect of betamethasone on DPSCs and stem cells from human exfoliated deciduous teeth (SHED) were evaluated.

Design: The proliferative effect of betamethasone on DPSCs was analyzed using a cholecystokinin octapeptide assay. The anti-inflammatory effect of betamethasone was investigated using quantitative polymerase chain reaction (qPCR) and ELISA. The anti-inflammatory mechanism was explored using qPCR, Western blot, and immunofluorescence staining. The osteo-/odontogenic differentiation and osteoclast effect of betamethasone on DPSCs and SHED were detected by qPCR.

Results: 1 μg L-1 betamethasone was found to have the strongest effect on DPSCs proliferation. The expression of pro-inflammatory cytokines and mediators, as well as prostaglandin E2 (PGE2) were significantly decreased following treatment with betamethasone in LPS- stimulated DPSCs. They were also decreased in response to an NF-κB inhibitor, Bay 11-7082. Betamethasone and Bay 11-7082 significantly inhibited the expression of p-p65 and promoted the nuclear exclusion of p65. Gene expression associated with osteo-/odontogenic differentiation was significantly up-regulated in betamethasone and osteogenic media (OM) treated groups. The ratio of the receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) at the mRNA level was suppressed in DPSCs and elevated in SHED.

Conclusions: Betamethasone has an anti-inflammatory effect on LPS- stimulated DPSCs through a blockade of NF-κB activation and exhibits an osteo-/odonto-inductive effect on DPSCs and SHED. Although betamethasone displays an osteoclast effect on SHED.

Keywords: NF-κB; betamethasone; dental pulp cells; inflammation.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Betamethasone / antagonists & inhibitors*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Dental Pulp / cytology
  • Dental Pulp / drug effects*
  • Dinoprostone / metabolism
  • Epithelial Cells / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Lipopolysaccharides / adverse effects*
  • NF-kappa B / drug effects*
  • NF-kappa B / metabolism*
  • Odontogenesis / drug effects
  • Osteoclasts / drug effects
  • Osteogenesis / drug effects
  • Osteoprotegerin / metabolism
  • RANK Ligand / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects*
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Tooth, Deciduous
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Osteoprotegerin
  • RANK Ligand
  • RELA protein, human
  • RNA, Messenger
  • TNFSF11 protein, human
  • Transcription Factor RelA
  • Betamethasone
  • Dinoprostone