Chronic binge alcohol-related differential expression also had significant effects on cellular pathways (Fig. 4). Canonical Wnt signaling is notable within this group because of its involvement in bone formation, recently uncovered based on the discovery that both loss-of-function and gain-of-function mutations occurring in the low-density lipoprotein receptor (LDLR)-related protein 5 (Lrp5), a Wnt co-receptor, are responsible for 2 rare hereditary conditions in humans; Osteoporosis pseudo-glioma syndrome (OPPG) a Lrp5 loss-of-function mutation resulting in early onset osteoporosis (Gong et al., 2001) and the high bone mass (HBM) phenotype Lrp5 gain-of function mutation resulting in hereditary increased bone mass (Boyden et al., 2002). We found that Lrp5 expression was significantly decreased in bone after binge alcohol exposure, as were the expression of several other Wnt-related genes. Other canonical Wnt pathway-related genes of note exhibiting decreased expression following chronic binge alcohol treatment include 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
