FoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation.

ABSTRACT: Besides their cell-damaging effects in the setting of oxidative stress, reactive oxygen species (ROS) play an important role in physiological intracellular signalling by triggering proliferation and survival. FoxO transcription factors counteract ROS generation by upregulating antioxidant enzymes. Here we show that intracellular H2O2 accumulation is a critical and purposeful adaptation for the differentiation and survival of osteoclasts, the bone cells responsible for the resorption of mineralized bone matrix. Using mice with conditional loss or gain of FoxO transcription factor function, or mitochondria-targeted catalase in osteoclasts, we demonstrate this is achieved, at least in part, by downregulating the H2O2-inactivating enzyme catalase. Catalase downregulation results from the repre

SUBMITTER: Bartell SM 

PROVIDER: S-EPMC4015330 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature