β-catenin (ctnnb1), and Dickkopf-1 (Dkk1). β-catenin, referred to as the molecular node of the canonical Wnt pathway (Glass and Karsenty, 2006) plays a pivotal role in Wnt signal transduction to the nucleus and transcription of canonical Wnt-regulated genes. The significant decrease observed in the expression of Dkk1, a Wnt inhibitor (Glass and Karsenty, 2006) does not fit the overall pattern observed of depression of canonical Wnt signaling by alcohol, but could possibly represent a feedback mechanism activated in bone to increase canonical Wnt signaling activity in response to the repressive effects of alcohol on Lrp5 and β-catenin, similar to the feedback loop observed recently in Lrp6/β-catenin signaling (Khan et al., 2007). Disruption of bone-related Wnt signaling could represent a novel mechanism of action responsible for alcohol-related depression of bone formation and resulting osteopenia observed in rodent chronic alcohol exposure models (Wezeman et al., 1999). The connection between alcohol-related bone damage and modulation of the canonical Wnt signaling pathway identified in this study is important because it provides a candidate molecular mechanism responsible for alcohol’s suppressive effect on bone formation, long believed to be an underlying cause of alcohol-related osteopenia (Farley et al., 1985).
