MicroRNA-145 Mediates Steroid-Induced Necrosis of the Femoral Head by Targeting the OPG/RANK/RANKL Signaling Pathway

PLoS One. 2016 Jul 26;11(7):e0159805. doi: 10.1371/journal.pone.0159805. eCollection 2016.

Abstract

Objective: To investigate the role of microRNA-145 (miR-145) in steroid-induced necrosis of the femoral head (SINFH) by evaluating its effects on the OPG/RANK/RANKL signaling pathway.

Methods: A rat model of SINFH was constructed via injection of the lentiviral vector pLV-shRNA-miR-145. Pathological observation was performed via tartrate-resistant acid phosphatase (TRAP) staining, and serum OPG levels were detected by ELISA. The mRNA expression levels of miR-145, OPG, RANK and RANKL in THP-1 cells were assessed by RT-PCR, and the protein expression levels of OPG, RANK and RANKL were assessed by western blotting.

Results: The expression of miR-145 in the lentivirus-mediated miR-145 group was significantly up-regulated compared with that in the control and normal groups (both P < 0.01). Serum OPG levels were decreased in SINFH rats compared with control and normal rats. The mRNA and protein expression levels of OPG in THP-1 cells decreased after transfection (all P < 0.05). By contrast, the mRNA and protein expression levels of RANK and RANKL in THP-1 cells increased after transfection (all P < 0.05). After transfection of 293T cells with an miR-145 overexpression vector, miR-145 expression in 293T cells increased significantly, while OPG mRNA and protein expression decreased significantly (all P < 0.05).

Conclusion: MiR-145 plays a role in the occurrence of SINFH by targeting the OPG/RANK/RANKL signaling pathway.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Femur Head Necrosis / etiology
  • Femur Head Necrosis / metabolism*
  • HEK293 Cells
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Osteoprotegerin / genetics
  • Osteoprotegerin / metabolism*
  • RANK Ligand / genetics
  • RANK Ligand / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Activator of Nuclear Factor-kappa B / genetics
  • Receptor Activator of Nuclear Factor-kappa B / metabolism*
  • Signal Transduction
  • Steroids / toxicity

Substances

  • MIRN145 microRNA, rat
  • MicroRNAs
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Steroids
  • Tnfrsf11b protein, rat

Grants and funding

The authors have no support or funding to report.