MicroRNA-34a alleviates steroid-induced avascular necrosis of femoral head by targeting Tgif2 through OPG/RANK/RANKL signaling pathway

Exp Biol Med (Maywood). 2017 Jun;242(12):1234-1243. doi: 10.1177/1535370217703975. Epub 2017 Apr 28.

Abstract

The study aims to investigate the effect of microRNA-34a (miR-34a) targeting Tgif2 on steroid-induced avascular necrosis of femoral head (SANFH) by regulating OPG/RANK/RANKL signaling pathway. SD rats were divided into normal control and model (RNAKL rat models) groups. The model group was further assigned into model control, negative control, miR-34a mimics and miR-34a inhibitors groups. QRT-PCR was applied to detect miR-34a, Tgif2, OPG, RANK and RNAKL mRNA expressions. Femoral head tissues were collected for Micro-CT scanning and HE staining. QRT-PCR and Western blotting were used to detect expressions of miR-34a, Tgif2, OPG, RANK, RANKL and Runx2, OPN and OC in bone tissues. Dual-luciferase reporter gene assay was used to testify the target relationship between miR-34a and Tgif2. Compared with the normal control group, the model group showed increased Tgif2, RANK and RANKL mRNA expressions, but decreased miR-34a and OPG mRNA expressions. Tgif2 mRNA expression was negatively correlated with miR-34a and OPG mRNA expressions. Micro-CT showed cystic degeneration of femoral head, with decreased bone volume/total volume (BV/TV), bone surface area/bone volume and trabecular number in the model control group compared with the normal control group. Compared with the model control group, the miR-34a mimics group showed increased BV/TV and trabecular thickness and Runx2, OPN and OC expressions, while the parameters decreased in the miR-34a inhibitors group. Compared with the normal control group, the other groups showed increased Tgif2, RANK and RANKL expressions but decreased miR-34a and OPG expressions. Compared with the model control group, Tgif2, RANK and RANKL expressions decreased and miR-34a and OPG expressions increased in the miR-34a mimics group, while the miR-34a inhibitors group had a reverse trend in contrast to the miR-34a mimics group. Tgif2 is a target gene of miR-34a. In conclusion, miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway. Impact statement miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway, which can be used as a new theoretical basis for SANFH treatment.

Keywords: MiR-34a; osteoprotegerin; receptor activator of nuclear factor Kappa B; receptor activator of nuclear factor Kappa ligand; signaling pathway; steroid-induced avascular necrosis of femoral head.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Femur Head Necrosis / chemically induced
  • Femur Head Necrosis / metabolism*
  • Gene Expression Regulation / drug effects*
  • Glucocorticoids / toxicity
  • Homeodomain Proteins / metabolism*
  • Male
  • Methylprednisolone / toxicity
  • MicroRNAs / metabolism*
  • MicroRNAs / pharmacology
  • Osteoprotegerin / metabolism
  • RANK Ligand / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Activator of Nuclear Factor-kappa B / metabolism
  • Repressor Proteins / metabolism*
  • Signal Transduction / drug effects

Substances

  • Glucocorticoids
  • Homeodomain Proteins
  • MicroRNAs
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Repressor Proteins
  • Tnfrsf11b protein, rat
  • Methylprednisolone