Involvement of osteopontin as a core protein in cholesterol gallstone formation

Background and purpose Matrix proteins are considered to be essential for biomineralization and to be important factors in the formation and growth of gallstones. Osteopontin (Opn) is a noncollagenous, acidic bone‐matrix glycoprotein, which is sialated and phosphorylated and which has a cell‐binding peptide sequence of glycine–arginine–glycine–aspartate–serine (GRGDS). To investigate the role of Opn in cholesterol gallstone formation, we have studied the involvement of Opn in cholesterol gallstone formation in the human gallbladder wall, in the stones, and in the mouse gallbladder using a gallstone experimental model. Methods Immunohistochemical staining was used in the human gallbladder wall and human gallstones and the determination of mRNA expression by reverse transcriptase‐PCR was used in the mouse gallbladder of a gallstone experimental model. Results The epithelium of stone‐laden gallbladders demonstrated high Opn reactivity, as did the core of the stones. Microscopically detected early stones without macroscopic evidence of lithiasis showed the same immunoreactivity as larger stones. Stone‐laden gallbladders were infiltrated by macrophages showing intense Opn expression. In gallstone‐forming mice, the expression of Opn mRNA and its protein were significantly increased in the gallbladder wall in the early phase of a lithogenic diet intake, before the initiation of inflammation. Conclusion These results suggest that Opn is possibly involved as a core protein in the formation of cholesterol gallstones.