オステオポンチンの遺伝子組換えによる尿路結石形成機序の解明と分子標的治療への応用 (第59回日本泌尿器科学会中部総会)

Abstract

Osteopontin (OPN) has been described to play a nonredundant role in the formation of renal crystals. This biological activity of OPN may be attributed to its characteristic structure, which includes 2 calciumbinding sites, Arg-Gly-Asp (RGD) sequences. To test this hypothesis, we evaluated wild-type mice (WT group), OPN-knockout mice (KO group), and two types of transgenic mice : (1) one type carrying a transgene in which the sequences coding for the 2 calcium-binding sites of the OPN were deleted (CaX group) and (2) the other type carrying a transgene in which the sequence that codes for the RGD sequence of the OPN was modified to one that codes for Arg-Gly-Glu (RGE ; RGE group). Changes occurring after intraperitoneal injection of glyoxylate for 9 d were analyzed. The amount of crystals deposited was the greatest in mice of the WT group and the least in those of the KO group. The number of crystal deposits in mice of the RGE and KO groups was approximately the same. Microscopic observations revealed that the crystal nuclei in mice in the CaX group were stratified and exhibited a disordered pattern ; this pattern was dissimilar to that observed in the mice in the WT and RGE groups, wherein the crystal nuclei exhibited a rosette petal-like radial pattern. The results indicate the possibility that each domain contributes to the mechanism by which OPN stimulates crystal formation.