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MiR-361-3p/Nfat5 Signaling Axis Controls Cementoblast Differentiation.

H Q Liao1, H Liu1,2, H L Sun1,2

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Journal of Dental Research
|July 26, 2019
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Summary

MicroRNAs (miRNAs) regulate cementoblast differentiation. miR-361-3p inhibits this process by targeting Nfat5, impacting key signaling pathways involved in periodontal tissue development.

Keywords:
cell differentiationcementogenesisdental cementummicroRNAssignal transductiontranscription factors

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Area of Science:

  • Periodontal tissue engineering
  • Molecular and cellular biology
  • Gene regulation

Background:

  • Periodontal tissue development involves complex cementoblast proliferation and differentiation processes.
  • MicroRNAs (miRNAs) are critical regulators of gene expression in biological systems.
  • The specific roles of miRNAs in cementoblast differentiation are not fully understood.

Purpose of the Study:

  • To investigate the role of microRNAs in regulating cementoblast proliferation and differentiation.
  • To identify specific miRNAs and their targets involved in these processes.
  • To elucidate the molecular mechanisms underlying miRNA-mediated regulation of cementoblast differentiation.

Main Methods:

  • MicroRNA microarray profiling to identify differentially expressed miRNAs.
  • Overexpression and inhibition of miR-361-3p in cementoblasts.
  • Bioinformatic analysis and dual luciferase assays to identify miRNA targets.
  • In vitro and in vivo validation of target gene expression.
  • Analysis of key intracellular signaling pathways (Erk1/2, JNK, p38, PI3K-Akt, NF-κB, Wnt/ß-catenin).

Main Results:

  • miR-361-3p expression decreased during cementoblast differentiation.
  • Overexpression of miR-361-3p inhibited cementoblast differentiation; inhibition promoted it.
  • Nuclear factor of activated T-cell 5 (Nfat5) was identified as a direct target of miR-361-3p.
  • Nfat5 knockdown mimicked the inhibitory effects of miR-361-3p.
  • miR-361-3p/Nfat5 axis modulated Erk1/2, PI3K-Akt, JNK, p38, NF-κB, and Wnt/ß-catenin signaling pathways.

Conclusions:

  • miR-361-3p acts as a negative regulator of cementoblast differentiation.
  • The miR-361-3p/Nfat5 signaling axis plays a crucial role in regulating cementoblast differentiation.
  • This axis influences multiple signaling pathways, including Erk1/2, PI3K-Akt, JNK, p38, NF-κB, and Wnt/ß-catenin.
  • Understanding this pathway offers potential therapeutic targets for periodontal regeneration.