ATF5介导的线粒体UPR抑制牙龈卟啉单胞菌LPS处理的成骨细胞中的RANKL

Abstract

Objective The purpose of this study was to investigate whether mitochondrial unfolded protein response (UPR mt ) was induced in Porphyromonas gingivalis -lipopolysaccharide ( P. gingivalis -LPS)-treated osteoblasts and to study the relationship among UPR mt , mitochondrial function and bone resorption in periodontitis. Design Osteoblasts were treated with P.gingivalis -LPS. Nicotinamide riboside (NR) and doxycycline (DOX) were used to enhance UPR mt , while small interference RNA was transfected to knock down activating transcription factor 5 (ATF5). Protein and mRNA levels of genes involved in UPR mt and bone metabolism were measured. Intracellular reactive oxygen species (ROS), mitochondrial ROS and mitochondrial membrane potential were detected by flow cytometry and confocal imaging. Results UPR mt and receptor activator of NF-κB ligand (RANKL) expression were induced in P. gingivalis -LPS-treated osteoblasts. Enhancement of UPR mt by NR or DOX decreased RANKL and RANKL/osteoprotegerin (OPG) ratio in osteoblasts. UPR mt inhibition by ATF5 knockdown aggravated mitochondrial dysfunction and promoted RANKL expression in P.gingivalis -LPS-treated osteoblasts. Conclusions ATF5-mediated UPR mt regulates RANKL expression through mtROS and mitochondrial membrane potential. UPR mt could be a potential target involved in the regulation of bone resorption in periodontitis.