Mitochondrial XXXX in osteocytes perturbs canalicular networks in the setting of age-related osteoporosis.

@entity6453 @entity19 @entity604 @entity5271 @entity2331 @entity183 @entity224
Osteocytes are major bone cells that play a crucial role in maintaining the quality of and healing damage to bone tissue. The number of living osteocytes and canalicular networks declines in an age-dependent manner. However, the pathological effects of mitochondrial redox imbalances on osteocytes and bone metabolism have not been fully elucidated. We generated @entity19 lacking mitochondrial @entity224 dismutase 2 ( @entity183 ) in osteocytes. Like an aged bone, @entity183 depletion in the osteocytes positively enhanced the production of cellular @entity224 in vivo. A bone morphological analysis demonstrated that the @entity183 -deficient femurs showed remarkable @entity604 in an age-dependent manner. Interestingly, @entity183 loss induced markedly disorganized osteocytic canalicular networks and decreased the number of live osteocytes. Furthermore, @entity183 deficiency significantly suppressed bone formation and increased bone resorption concomitant with the upregulation of sclerostin and receptor activator of NF-kB ligand ( @entity5271 ). In vitro experiments also revealed that treatment with @entity6453 , a @entity224 inducer in mitochondria, promoted the @entity5271 expression via, in part, ERK phosphorylation. These findings demonstrate that the mitochondrial @entity224 induced in osteocytes by @entity183 ablation causes age-related @entity604 due to the @entity2331 via the deregulation of the sclerostin and @entity5271 expression.
