Osteopontin plays an anti‐nucleation role in cholesterol gallstone formation

Abstract

To investigate the role of osteopontin in cholesterol gallstone formation. Nucleation time was determined in model and human gallbladder bile in vitro. Effect of osteopontin on vesicles of bile was investigated via transmission electron microscopy. The mRNA and protein expression of osteopontin were detected in human calculus and normal gallbladder tissues, and then lipid compositions of human bile were determined via commercial kits. Osteopontin could prolong the nucleation time in a dose-dependent manner, and inhibit the pro-nucleation effect induced by calcium ion. Cholesterol crystal growth was inhibited by osteopontin in a dose-dependent manner in model and human gallbladder bile, but not affected by calcium. Furthermore, the formation, aggregation and fusion of vesicles were suppressed by osteopontin in model and human bile as demonstrated by transmission electron microscopy. The mRNA and protein expression of osteopontin in calculus gallbladder tissues were lower than those in normal tissues. The concentrations of cholesterol, phospholipid and bile acids, and cholesterol saturated index were higher and the contents of osteopontin and calcium, nevertheless, were found to be lower in lithogenic bile than those in normal controls. These findings indicated that osteopontin could inhibit the cholesterol gallstone formation as an anti-nucleation factor, which may be involved in the pathogenesis of cholesterol gallstone formation.