Advanced oxidation protein products induce pre-osteoblast apoptosis through a nicotinamide adenine dinucleotide phosphate oxidase-dependent, mitogen-activated protein kinases-mediated intrinsic apoptosis pathway.
Aging Cell
; 17(4): e12764, 2018 08.
Article
en En
| MEDLINE
| ID: mdl-29659123
ABSTRACT
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 that AOPP accumulation was correlated with age-related bone loss. However, the effect of AOPPs on the osteoblast apoptosis still remains unknown. Exposure of osteoblastic MC3T3-E1 cells to AOPPs caused the excessive generation of reactive oxygen species (ROS) by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Increased ROS induced 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. Chronic AOPP loading in aged Sprague-Dawley rats induced osteoblast apoptosis and activated NADPH oxidase signaling cascade, in combination with accelerated bone loss and deteriorated bone microstructure. Our study suggests that AOPPs induce osteoblast apoptosis by the NADPH oxidase-dependent, MAPK-mediated intrinsic apoptosis pathway.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Osteoblastos
/
Apoptosis
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NADPH Oxidasas
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Proteínas Quinasas Activadas por Mitógenos
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Productos Avanzados de Oxidación de Proteínas
Límite:
Animals
Idioma:
En
Revista:
Aging Cell
Año:
2018
Tipo del documento:
Article
País de afiliación:
China