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United States Department of Agriculture

Agricultural Research Service

Research Project: IMPACT OF EARLY DIETARY FACTORS ON CHILD DEVELOPMENT AND HEALTH Title: ROS/redox signaling regulates bone turnover in an age-specific manner in female mice

item Mercer, Kelly -
item Suva, Larry -
item Badger, Thomas
item Chen, Jinran -
item Ronis, Martin -

Submitted to: Journal of Bone and Mineral Research
Publication Type: Abstract Only
Publication Acceptance Date: July 1, 2012
Publication Date: January 10, 2013
Citation: Mercer, K., Suva, L., Badger, T.M., Chen, J., Ronis, M.J. 2013. ROS/redox signaling regulates bone turnover in an age-specific manner in female mice [abstract]. Journal of Bone and Mineral Research. 27(Issue Supplement 1):

Technical Abstract: In bone, oxidant signaling through NADPH oxidase (NOX)-derived reactive oxygen species (ROS) superoxide and/or hydrogen peroxide appears to be an important stimulus for osteoclast differentiation and activity. ROS signaling has been suggested to increase RANKL mRNA and protein expression, thus enhancing osteoclastogenic RANKL-RANK signaling between osteoblasts and osteoclast precursors. We have previously demonstrated that chronic alcohol abuse (EtOH) generates excess Nox-dependent ROS in osteoblasts, which functions to inhibit bone formation through impairment of Wnt signaling, and increases osteoclastogenesis by stimulating RANKL-RANK signaling. These effects can be blocked by the dietary antioxidant N-acetylcysteine and the pan-Nox inhibitor DPI. In the current study we utilized a well-described transgenic C57Bl/6J mouse strain that over-expresses human catalase (TgCAT) in all tissues to see if limiting excess hydrogen peroxide production in bone would protect against EtOH-mediated bone loss. MicroCT analysis of chow fed TgCAT mice at 6 wks revealed an osteopetrotic phenotype, increased %BV/TV, number and decreased spacing, p<0.05. Six-wk-old, wild-type (WT) and TgCAT female mice were then given rodent chow ad libitum, or pair-fed (PF) liquid diets with 0% or 30% EtOH calories for 8 weeks. In WT mice at age 14 weeks, PF had no effect on bone parametrers relative to ad libitum chow feeding, but EtOH-feeding significantly reduced trabecular %BV/TV, and number and increased spacing in tibial bone, p<0.05. EtOH consumption also decreased cortical cross-sectional area and thickness (p<0.05) in WT mice compared to PF controls, p<0.05. At 14 wks, we observed significant reductions in %BV/TV, and number, and increases in spacing and thickness in ad libitum chow fed and in PF TgCAT mice compared to WT chow fed and PF mice, p<0.05, suggestive of an osteoporotic phenotype associated with TgCAT overexpression later in development. EtOH-feeding had no further effect on bone parameters in TgCAT mice. In conclusion, over-expression of human catalase in TgCAT mice produced significantly greater bone mass than WT mice at 6 wks and lower bone mass at 14 wks. EtOH-feeding resulted in reductions in trabecular and cortical bone in WT mice but no additional reductions in trabecular or cortical bone parameters in TgCAT mice. These data suggest that ROS/redox signaling regulates bone turnover in an age-dependent fashion.

Last Modified: 11/24/2015
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