Inhibition of PERK Signaling Prevents Against Glucocorticoid-induced Endotheliocyte Apoptosis and Osteonecrosis of the Femoral Head
Yanchun Gao, Hongyi Zhu, Qiyang Wang, Yong Feng, Changqing Zhang
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.
Topics & Concepts
ApoptosisUnfolded protein responseDownregulation and upregulationCHOPFemoral headEndoplasmic reticulumIn vivoMedicineGlucocorticoidCancer researchIn vitroCell biologyChemistryEndocrinologyBiologyGeneAnatomyBiochemistryBiotechnologyEndoplasmic Reticulum Stress and DiseaseAutophagy in Disease and TherapyAdenosine and Purinergic Signaling