of a significant number of genes involved in integrin signaling, including a significant increase in mRNA levels of β3 integrin (Itgb3). Given the promiscuous nature of integrin heterodimer formation (Teitelbaum, 2005) an alcohol-related increase in β3 mRNA levels could increase the formation of the αvβ3 heterodimer in osteoclasts, enhancing both αvβ3-mediated matrix attachment and intracellular signaling, leading to the organization of the osteoclast cytosketeton and formation of the protected resorptive microenvironment required for bone resorption. The significant decreases in β3 and other integrin signaling-related genes we observed after chronic binge alcohol treatment suggests that a temporal profile of alcohol-related effects on integrin gene expression may exist in bone tissue. The finding that β3 integrin expression and other key genes in the integrin signaling pathway are potential bone-specific targets of alcohol may represent a novel mechanism underlying an alcohol-mediated modulation of bone resorption.
