Effects of Impaired Functional Domains of Osteopontin on Renal Crystal Formation: Analyses of OPN Transgenic and OPN Knockout Mice
Effects of Impaired Functional Domains of Osteopontin on Renal Crystal Formation: Analyses of OPN Transgenic and OPN Knockout Mice
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DOI：
10.1359/jbmr.090520
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发表时间：
2010-12-01
影响因子：
6.2
通讯作者：
Kohri, Kenjiro
中科院分区：
文献类型：
--
作者：
Hamamoto, Shuzo;Nomura, Shintaro;Kohri, Kenjiro
骨桥蛋白 (OPN) 被描述为在肾晶体形成中发挥非冗余作用在这里，我们研究了 OPN 受损结构域，即精氨酸-甘氨酸-天冬氨酸 (RGD) 序列和两个钙结合位点对晶体形成的影响。删除两个钙结合位点（CaX组）腹腔注射乙醛酸9天后，分析晶体形成三个参数（定位、数量和微观结构）发生的变化。WT组中，晶体沉积在肾皮质髓质交界处逐渐有序地增加，而KO组中则在肾皮质中零星观察到晶体沉积。CaX组和RGE组中，沉积都集中在皮质髓质附近。结 晶沉积在 WT 组中最多，在 KO 组中最少 RGE 组中的沉积数量与 KO 组中几乎相等 镜下观察显示，CaX 组中的晶核呈分层且以无序的形式出现，这种模式与 WT 组中的不同，可以观察到玫瑰花瓣状的放射状图案 在 RGE 组中，可以观察到与 WT 组中相似的放射状图案。每个结构域都有助于 OPN 刺激晶体形成的机制 (C) 2010 年美国骨与矿物质研究学会
Osteopontin (OPN) has been described as playing a nonredundant role in renal crystal formation Here we investigated the effects of impaired domains of OPN, namely, the Arg-Gly-Asp (RGD) sequence and two calcium-binding sites on crystal formation We used wildtype mice (WT group), OPN knockout mice (KO group), and OPN knockout mice carrying either a transgene in which the RGD sequence had been modified to Arg-Gly-Glu (RGE group) or whose two calcium-binding sites had been deleted (CaX group) Following intraperitoneal injection of glyoxylate for 9 days, the changes occurring in three parameters of crystal formation-localization, number, and microstructure-were analyzed In the WT group, crystal deposits increased gradually at the renal corticomedullary junction in an orderly fashion, whereas those in the KO group were observed sporadically in the renal cortex In both the CaX and RGE groups, deposits were localized near the corticomedullary junction Crystal deposition was greatest in the WT group and least in the KO group The number of deposits in the RGE group was nearly equal to that in the KO group Microscopic observations revealed that the crystal nuclei in the CaX group were stratified and occurred in a disordered pattern, this pattern was dissimilar to that in the WT group, in which a rosette petal-like radial pattern was observed In the RGE group, the nuclei exhibited a radial pattern similar to that in the WT group The results indicated the possibility that each domain contributes to the mechanism by which OPN stimulates crystal formation (C) 2010 American Society for Bone and Mineral Research