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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #246851
Title: A crucial role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of wnt/beta-catenin signaling

Author
item CHEN, JINRAN - Arkansas Children'S Nutrition Research Center (ACNC)
item LAZARENKO, OXANA - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)
item BLACKBURN, MICHAEL - Arkansas Children'S Nutrition Research Center (ACNC)
item Badger, Thomas - Arkansas Children'S Nutrition Research Center (ACNC)
item RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/10/2009
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Female skeletal responses to ethanol may vary depending on the physiologic status (viz. cycling, pregnancy, lactation). Nonetheless, ethanol-induced oxidative stress appears to be the key event leading to skeletal toxicity. In the current study, we chronically infused EtOH-containing liquid diets (12 g/kg/day) to post-lactational female SD rat dams for 4 wk beginning at weaning using total enteral nutrition. EtOH decreased bone mineral density (BMD) compared to control animals during this period of post-lactational bone rebuilding. Bone loss and redution of bone formation markers was completely blocked by co-administration of the antioxicant N-acetylcysteine (NAC) at 1.2 g/kg/d. Expression of Wnt signaling components were down-regulated by EtOH. Protein expression of the key canonical Wnt signaling molecule, beta-catenin was inhibited while glycogen synthase kinase-3-beta was de-phosphorylated by EtOH in bone and pre-osteoblastic cells, this was blocked by NAC. EtOH trans-inactivated TCF/LEF target gene transcription and eliminated beta-catenin nuclear translocation in osteoblasts. In addition, EtOH reciprocally suppressed osteoblastogenesis and enhanced adipogenesis. Effects of EtOH on lineage commitment of mesenchymal stromal cells were eliminated by NAC. These oservations suggest that EtOH inhibits bone formation through stimulation of oxidative stress leading to suppressed Wnt/Beta-catenin signaling in female post-lactational rats.