miR-140-5p-mediated regulation of the proliferation and differentiation of human dental pulp stem cells occurs through the lipopolysaccharide/toll-like receptor 4 signaling pathway

Eur J Oral Sci. 2017 Dec;125(6):419-425. doi: 10.1111/eos.12384.

Abstract

Human dental pulp stem cells (DPSCs) are oral mesenchymal stem cells with potential to differentiate into various cell types. Recent studies of DPSCs have focused on microRNAs (miRNAs), a class of small noncoding RNAs that play crucial roles in regulating DPSC phenotypes. In the current study, the expression of miR-140-5p was significantly decreased during lipopolysaccharide (LPS)-mediated differentiation of DPSCs in vitro. Overexpression of miR-140-5p enhanced proliferation of DPSCs and inhibited DPSC differentiation, whereas suppression of miR-140-5p produced the opposite effect. Moreover, the expression of toll-like receptor 4 (TLR-4), a critical regulator of DPSCs, was negatively correlated with the levels of miR-140-5p. A luciferase reporter analysis confirmed that miR-140-5p could regulate TLR-4 by directly binding to the 3'-untranslated region (3'-UTR) of the TLR4 mRNA. Additionally, we suppressed TLR-4 expression by treating cells with a TLR-4 inhibitor, CLI-095, and demonstrated that the effect of the miR-140-5p inhibitor on DPSC proliferation and differentiation could be partially reversed by blocking TLR-4. Taken together, our data suggest that miR-140-5p is a novel miRNA that regulates DPSC proliferation and differentiation.

Keywords: lipopolysaccharide; microRNA, oral mesenchymal stem cells; small noncoding RNAs.

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Cell Cycle
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics*
  • Cell Survival
  • Cells, Cultured
  • Dental Pulp / cytology*
  • Humans
  • In Vitro Techniques
  • Lipopolysaccharides
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics*
  • Odontoblasts / metabolism*
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics*
  • Toll-Like Receptor 4 / genetics*

Substances

  • Lipopolysaccharides
  • MicroRNAs
  • Toll-Like Receptor 4