p47phox-Nox2-dependent ROS Signaling Inhibits Early Bone Development in Mice but Protects against Skeletal Aging

摘要: Abstract Bone remodeling is age-dependently regulated and changes dramatically during the course of development. Progressive accumulation reactive oxygen species (ROS) has been suspected to be leading cause many inflammatory degenerative diseases, as well an important factor underlying effects aging. In contrast, how reduced ROS signaling regulates inflammation in bone remains unknown. Here, we utilized a p47phox knock-out mouse model, which essential cytosolic co-activator Nox2 lost, characterize metabolism at 6 weeks 2 years age. Compared with their age-matched wild type controls, loss function p47phox−/− mice resulted age-related switch mass strength. Differences were associated increased formation 6-week-old but decreased 2-year-old mice. Despite decreases generation marrow cells p47phox-Nox2 osteoblastic cells, showed senescence-associated secretory phenotype compared controls. These vivo findings mechanistically recapitulated ex cell culture primary fetal calvarial from accelerated senescence pathway accompanied by inflammation. data indicate that observed p47phox-deficient occurs through milieu p47phox-Nox2-dependent physiological suppresses