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MiR-202-3p regulates interleukin-1β-induced expression of matrix metalloproteinase 1 in human nucleus pulposus

Changgui Shi1, Lecheng Wu1, Wenbo Lin1

  • 1Department of Orthopedics, Changzheng Hospital, Second Military Medical University of China, Shanghai, China.

Gene
|November 21, 2018
PubMed

Insights

MicroRNA-202-3p regulates matrix metalloproteinase-1 in degenerating intervertebral discs. Lower miR-202-3p levels correlate with increased MMP-1, suggesting its role in disc degeneration.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • RNA Biology

Background:

  • Intervertebral disc degeneration (IVDD) involves complex molecular changes.
  • MicroRNAs (miRNAs) are key regulators implicated in IVDD pathogenesis.
  • Matrix metalloproteinase-1 (MMP-1) is a critical enzyme in extracellular matrix degradation during IVDD.

Purpose of the Study:

  • To investigate the role of miR-202-3p in interleukin-1β (IL-1β)-induced MMP-1 expression in human nucleus pulposus (NP) cells.
  • To elucidate the regulatory mechanism of miR-202-3p on MMP-1 during intervertebral disc degeneration.

Main Methods:

  • Human NP cells were stimulated with IL-1β in vitro.
  • MicroRNA arrays and bioinformatics were used to identify miRNA expression profiles and targets.
  • Quantitative real-time PCR, Western blotting, and reporter assays were employed to assess gene and protein expression.
  • Functional assays evaluated the impact of miR-202-3p on type II collagen degradation.

Main Results:

  • IL-1β stimulation led to down-regulation of miR-202-3p and up-regulation of MMP-1 in NP cells.
  • Reduced miR-202-3p expression was observed in severe degenerative discs.
  • miR-202-3p directly suppressed IL-1β-induced MMP-1 production by binding to the MMP-1 3'-UTR.
  • miR-202-3p inhibited type II collagen degradation, an effect reversed by MMP-1 overexpression.

Conclusions:

  • miR-202-3p acts as a crucial negative regulator of MMP-1 in human nucleus pulposus cells.
  • The miR-202-3p/MMP-1 axis plays a significant role in the pathogenesis of intervertebral disc degeneration.
  • Targeting miR-202-3p may offer a therapeutic strategy for managing disc degeneration.
Keywords:
Interleukin-1βIntervertebral disc degenerationMatrix metalloproteinase 1MiR-202-3pMicroRNANucleus pulposusType II collagen

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