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miR-146a, an IL-1β responsive miRNA, induces vascular endothelial growth factor and chondrocyte apoptosis by

Jing Li1, Jingang Huang, Liming Dai

  • 1Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, China, 200025.

Arthritis Research & Therapy
|April 18, 2012
PubMed
Abstract

Insights

Osteoarthritis (OA) involves increased miR-146a, which upregulates VEGF and downregulates Smad4, impairing TGF-β signaling. This microRNA contributes to OA pathogenesis by promoting cartilage degradation and apoptosis.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Pathology

Background:

  • Osteoarthritis (OA) is characterized by differential expression of microRNAs (miRNAs), including miR-146a, in cartilage.
  • The precise role of miR-146a in the pathogenesis of OA remains unclear.
  • Identifying miR-146a targets is crucial for understanding its function in chondrocytes during OA development.

Purpose of the Study:

  • To identify a molecular target of miR-146a.
  • To elucidate the function of miR-146a in chondrocytes during OA pathogenesis.
  • To investigate the role of miR-146a in the transforming growth factor (TGF)-β signaling pathway and apoptosis.

Main Methods:

  • Primary chondrocytes and surgically induced OA rat models were utilized.
  • Expression levels of miR-146a, Smad4, and vascular endothelial growth factor (VEGF) were quantified using real-time PCR and western blotting/immunohistochemistry.
  • Luciferase reporter assays, extracellular signal-regulated kinase (ERK) assays, and TUNEL assays were performed to assess miR-146a's effects on TGF-β signaling and apoptosis.

Main Results:

  • Interleukin-1 beta (IL-1β) treatment increased miR-146a and VEGF, while decreasing Smad4 in chondrocytes.
  • Smad4 was identified as a direct target of miR-146a, mediating miR-146a's upregulation of VEGF.
  • miR-146a expression reduced chondrocyte responsiveness to TGF-β1 and increased apoptosis; OA cartilage showed elevated miR-146a and VEGF, with decreased Smad4.

Conclusions:

  • miR-146a is overexpressed in an experimental OA model and is responsive to IL-1β.
  • miR-146a contributes to OA pathogenesis by upregulating VEGF and inhibiting the TGF-β pathway via Smad4 targeting.
  • Targeting miR-146a may offer a therapeutic strategy for OA.

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