Another alcohol-related effect on bone formation potentially explained by a deactivation of canonical Wnt signaling includes effects on differentiation of mesenchymal progenitor cells. Signaling through Wnt/β-catenin appears to be required for the determination of mesenchymal progenitor cells toward an osteoblast or chondrocyte lineage (Hill et al., 2005). Canonical Wnt pathway activation also inhibits adipocyte differentiation from mesenchymal progenitors, further promoting the osteoblast lineage (Bennett et al., 2005). Thus, an alcohol-related inhibition of Wnt/β-catenin signaling could also provided a mechanistic explanation for the shift of bone marrow-derived mesenchymal stem cells (MSC) from an osteoblastic to an adipogenic lineage, recently observed in alcohol-exposed primary human and mouse MSC cultures (Cui et al., 2006, Wezeman and Gong, 2004) and for the in vivo development of alcohol-induced fatty bone marrow (Wang et al., 2003).
