TY - JOUR T1 - Reactive Oxygen Species Differentially Regulate Bone Turnover in an Age-Specific Manner in Catalase Transgenic Female Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.116.233213 SP - jpet.116.233213 AU - Alexander W Alund AU - Kelly E Mercer AU - Larry J Suva AU - Casey F Pulliam AU - Jin-Ran Chen AU - Thomas M Badger AU - Holly Van Remmen AU - Martin J.J. Ronis Y1 - 2016/01/01 UR - http://jpet.aspetjournals.org/content/early/2016/05/12/jpet.116.233213.abstract N2 - Chronic alcohol (EtOH) consumption results in reactive oxygen species (ROS) generation in bone and osteopenia, due to increased bone resorption and reduced bone formation. In this study, transgenic C57Bl/6J mice over-expressing human catalase (TgCAT) were used to test if limiting excess hydrogen peroxide would protect against EtOH-mediated bone loss. MicroCT analysis of the skeleton of 6 week old female chow-fed TgCAT mice revealed a high bone mass phenotype with increased cortical bone area and thickness as well as significantly increased trabecular bone volume (p<0.05). Six week old wild-type (WT) and TgCAT female mice were chow-fed, or pair-fed (PF) liquid diets with or without EtOH, approximately 30% of calories, for 8 weeks. Pair-feeding of WT had no demonstrable effect on the skeleton, however EtOH feeding of WT mice significantly reduced cortical and trabecular bone parameters along with bone strength compared to PF controls, (p<0.05). In contrast, EtOH feeding of TgCAT mice had no effect on trabecular bone compared to PF controls. At 14 weeks of age, there was significantly less trabecular bone and cortical cross sectional area in TgCAT mice than WT mice (p<0.05), suggesting impaired normal bone accrual with age. TgCAT mice expressed less Collagen1α and higher sclerostin mRNA, (p<0.05), suggesting decreased bone formation in TgCAT mice. In conclusion, catalase over-expression resulted in greater bone mass than WT mice at 6 wks and lower bone mass at 14 wks. EtOH-feeding induced significant reductions in bone architecture and strength in WT mice, but TgCAT mice were partially protected. These data implicate ROS signaling in the regulation of bone-turnover in an age-dependent manner and that excess hydrogen peroxide generation contributes to alcohol-induced osteopenia. ER -