miR-144-3p ameliorates the progression of osteoarthritis by targeting IL-1β: Potential therapeutic implications

J Cell Physiol. 2021 Oct;236(10):6988-7000. doi: 10.1002/jcp.30361. Epub 2021 Mar 27.

Abstract

The pro-inflammatory cytokine interleukin 1 beta (IL-1β) plays a critical role in osteoarthritis (OA) disease pathogenesis. MicroRNA (miRNA) activity is related to inflammation in OA and some miRNAs specifically regulate IL-mediated degradation of cartilage type II collagen. Previous studies have indicated that miR-144-3p is a useful target in the regulation of pro-inflammatory cytokines in different diseases. However, the role of miR-144-3p in OA is unclear. In this study, we observed a negative correlation between miR-144-3p and IL-1β expression in OA. miR-144-3p mimic transfection of OA synovial fibroblasts downregulated levels of IL-1β expression, while blocking the MAPK, PI3K/Akt, and NF-κB signaling pathways relating to IL-1β production, and effectively increased miR-144-3p expression in OASFs. Findings from an anterior cruciate ligament transection rat model revealed that administration of miR-144-3p mimic effectively ameliorated OA progression and reduced the numbers of IL-1β-positive cells in synovial tissue. This study suggests that miR-144-3p is a useful therapeutic target in OA disease.

Keywords: anterior cruciate ligament transection rat model; interleukin 1 beta; miR-144-3p; osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Case-Control Studies
  • Cells, Cultured
  • Databases, Genetic
  • Disease Models, Animal
  • Disease Progression
  • Down-Regulation
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Osteoarthritis / prevention & control
  • Osteoarthritis, Knee / genetics
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / pathology
  • Phosphatidylinositol 3-Kinase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology
  • Synoviocytes / metabolism*
  • Synoviocytes / pathology

Substances

  • IL1B protein, human
  • IL1B protein, rat
  • Interleukin-1beta
  • MIRN144 microRNA, human
  • MIRN144 microRNA, rat
  • MicroRNAs
  • NF-kappa B
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases