Inhibition of PERK Signaling Prevents Against Glucocorticoid-induced Endotheliocyte Apoptosis and Osteonecrosis of the Femoral Head

Int J Biol Sci. 2020 Jan 1;16(4):543-552. doi: 10.7150/ijbs.35256. eCollection 2020.

Abstract

Vascular injury is considered an important pathological process during glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). In this study, we tried to investigate whether the endoplasmic reticulum (ER) stress is triggered in the GC-induced endotheliocyte (EC) apoptosis and ONFH. The results showed that a GC upregulated the expression of ER stress-related proteins, and PERK-CHOP signaling played an important role and induced EC apoptosis. The inhibition of PERK by GSK2656157 significantly decreased the GC-induced EC apoptosis in vitro and in vivo, thus protecting a rat model from vascular injury and significantly preventing GC-induced ONFH.

Keywords: PERK signaling; apoptosis; endoplasmic-reticulum stress; endotheliocyte; glucocorticoid; osteonecrosis of femoral head.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Endoplasmic Reticulum Stress / drug effects
  • Femur Head / drug effects*
  • Femur Head / pathology*
  • Femur Head Necrosis / drug therapy*
  • Femur Head Necrosis / metabolism
  • Glucocorticoids / pharmacology*
  • Glucocorticoids / therapeutic use*
  • Immunohistochemistry
  • Indoles / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects

Substances

  • GSK2656157
  • Glucocorticoids
  • Indoles
  • Adenine