title: Reactive Oxygen Species Differentially Regulate Bone Turnover in an Age-Specific Manner in Catalase Transgenic Female Mice.
abstract: Chronic ethyl 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 overexpressing human catalase (TgCAT) were used to test whether limiting excess hydrogen peroxide would protect against EtOH-mediated bone loss. Micro-computed tomography analysis of the skeletons 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 with PF controls (P < 0.05). In contrast, EtOH feeding of TgCAT mice had no effect on trabecular bone compared with 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 overexpression resulted in greater bone mass than in WT mice at 6 weeks and lower bone mass at 14 weeks. 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 indicate that excess hydrogen peroxide generation contributes to alcohol-induced osteopenia.
authors.affiliation: Arkansas Children's Nutrition Center (A.W.A., K.E.M., J.-R.C., T.M.B.), Interdisciplinary Biomedical Sciences (A.W.A.), Department of Pediatrics (K.E.M., J.-R.C., T.M.B.), and Department of Orthopedic Surgery (L.J.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (C.F.P., M.J.J.R.); and Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma (H.V.R.).
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Alund
authors.affiliation: Arkansas Children's Nutrition Center (A.W.A., K.E.M., J.-R.C., T.M.B.), Interdisciplinary Biomedical Sciences (A.W.A.), Department of Pediatrics (K.E.M., J.-R.C., T.M.B.), and Department of Orthopedic Surgery (L.J.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (C.F.P., M.J.J.R.); and Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma (H.V.R.).
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Mercer
authors.affiliation: Arkansas Children's Nutrition Center (A.W.A., K.E.M., J.-R.C., T.M.B.), Interdisciplinary Biomedical Sciences (A.W.A.), Department of Pediatrics (K.E.M., J.-R.C., T.M.B.), and Department of Orthopedic Surgery (L.J.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (C.F.P., M.J.J.R.); and Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma (H.V.R.).
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Suva
authors.affiliation: Arkansas Children's Nutrition Center (A.W.A., K.E.M., J.-R.C., T.M.B.), Interdisciplinary Biomedical Sciences (A.W.A.), Department of Pediatrics (K.E.M., J.-R.C., T.M.B.), and Department of Orthopedic Surgery (L.J.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (C.F.P., M.J.J.R.); and Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma (H.V.R.).
authors.forename: Casey F
authors.initials: CF
authors.lastname: Pulliam
authors.affiliation: Arkansas Children's Nutrition Center (A.W.A., K.E.M., J.-R.C., T.M.B.), Interdisciplinary Biomedical Sciences (A.W.A.), Department of Pediatrics (K.E.M., J.-R.C., T.M.B.), and Department of Orthopedic Surgery (L.J.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (C.F.P., M.J.J.R.); and Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma (H.V.R.).
authors.forename: Jin-Ran
authors.initials: JR
authors.lastname: Chen
authors.affiliation: Arkansas Children's Nutrition Center (A.W.A., K.E.M., J.-R.C., T.M.B.), Interdisciplinary Biomedical Sciences (A.W.A.), Department of Pediatrics (K.E.M., J.-R.C., T.M.B.), and Department of Orthopedic Surgery (L.J.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (C.F.P., M.J.J.R.); and Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma (H.V.R.).
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Badger
authors.affiliation: Arkansas Children's Nutrition Center (A.W.A., K.E.M., J.-R.C., T.M.B.), Interdisciplinary Biomedical Sciences (A.W.A.), Department of Pediatrics (K.E.M., J.-R.C., T.M.B.), and Department of Orthopedic Surgery (L.J.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (C.F.P., M.J.J.R.); and Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma (H.V.R.).
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.affiliation: Arkansas Children's Nutrition Center (A.W.A., K.E.M., J.-R.C., T.M.B.), Interdisciplinary Biomedical Sciences (A.W.A.), Department of Pediatrics (K.E.M., J.-R.C., T.M.B.), and Department of Orthopedic Surgery (L.J.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas; Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana (C.F.P., M.J.J.R.); and Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma (H.V.R.) mronis@lsuhsc.edu.
authors.forename: Martin J J
authors.initials: MJ
authors.lastname: Ronis
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013977:Tibia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D017382:Reactive Oxygen Species; D000431:Ethanol; D006861:Hydrogen Peroxide; D002374:Catalase