Work

Advanced oxidation protein products induce pre‐osteoblast apoptosis through a nicotinamide adenine dinucleotide phosphate oxidase‐dependent, mitogen‐activated protein kinases‐mediated intrinsic apoptosis pathway

Year: 2018

Type: article

Abstract: Summary Osteoblast apoptosis contributes to age‐related bone loss. Advanced oxidation protein products (AOPPs) are recognized as the markers of oxidative stress and potent inducers of apoptosis. We have demonstrated thatAOPPaccumulation was correlated with age‐related bone loss. However, the effect ofAOPPs on the osteoblast apoptosis still remains unknown. Exposure of osteoblasticMC3T3‐E1 cells toAOPPs caused the excessive generation of reactive oxygen species (ROS) by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. IncreasedROSinduced phosphorylation of mitogen‐activated protein kinases (MAPKs), which subsequently triggered intrinsic apoptosis pathway by inducing mitochondrial dysfunction, endoplasmic reticulum stress, and Ca2+overload and eventually leads to apoptosis. ChronicAOPPloading in aged Sprague‐Dawley rats induced osteoblast apoptosis and activatedNADPHoxidase signaling cascade, in combination with accelerated bone loss and deteriorated bone microstructure. Our study suggests thatAOPPs induce osteoblast apoptosis by theNADPHoxidase‐dependent,MAPK‐mediated intrinsic apoptosis pathway.

Source: Aging Cell

DOI: 10.1111/acel.12764