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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #289518
Title: Role of NADPH oxidases and reactive oxygen species in regulation of bone turnover and the skeletal toxicity of alcohol

Author
item RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)
item MERCER, KELLEY - Arkansas Children'S Nutrition Research Center (ACNC)
item SUVA, LARRY - University Arkansas For Medical Sciences (UAMS)
item Badger, Thomas
item CHEN, JINRAN - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Toxicologist
Publication Type: Abstract Only
Publication Acceptance Date: 12/4/2012
Publication Date: 3/1/2013
Citation: Ronis, M.J., Mercer, K., Suva, L.J., Badger, T.M., Chen, J. 2013. Role of NADPH oxidases and reactive oxygen species in regulation of bone turnover and the skeletal toxicity of alcohol [abstract]. Toxicologist. 132(1):Abstract 1589, p. 340.

Interpretive Summary:

Technical Abstract: Recent studies with genetically modified mice and dietary antioxidants have suggested an important role for superoxide derived from NADPH oxidase (NOX) enzymes and other reactive oxygen species (ROS) such as hydrogen peroxide in regulation of normal bone turnover during development and also in the responses of the skeleton to toxicants such as ethanol (EtOH) which generate excess ROS in bone tissue. We have shown that EtOH causes bone loss as a result of NOX generated ROS, reduced bone formation via impaired Wnt-' catenin signaling and increased RANKL-dependent osteoclastogenesis. Buffering of anti-oxidant capacity though administration of the glutathione precursor N-acetylcysteine completely prevented EtOH-induced loss of bone mineral density, inhibiting both suppression of bone formation and increases in bone resorption. There was no apparent bone phenotype associated with genotype at age 3 mo in mice lacking the NOX co-factor p47phox and thus with impaired capacity to generate excess superoxide in response to EtOH. However, these mice were only protected from alcohol-stimulated increases in bone resorption. This was accompanied by inhibition of EtOH-associated increases in osteoclastogenesis and induction of RANKL. In mice where hydrogen peroxide concentration in bone is reduced as a result of transgenic expression of catalase, whereas 6-wk-old mice had increased trabecular bone, 3-mo-old mice had reduced trabecular bone and impaired osteoblastogenesis compared to wild type mice and were unprotected against ethanol actions. These data suggest that ROS signaling involving hydrogen peroxide is important in regulation of adult bone formation, but that excess production of superoxide via NOX as a result of exposure to toxicants such as EtOH can stimulate RANKL-dependent increases in bone resorption.