Morphological conversion of calcium oxalate crystals into stones is regulated by osteopontin in mouse kidney

Morphological conversion of calcium oxalate crystals into stones is regulated by osteopontin in mouse kidney
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DOI:
10.1359/jbmr.080514
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发表时间:
2008-10-01
影响因子:
6.2
通讯作者:
Kohri, Kenjiro
Kohri, Kenjiro
中科院分区:
医学1区
文献类型:
--
作者:
Okada, Atsushi;Nomura, Shintaro;Kohri, Kenjiro

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肾结石形成的一个重要过程是将肾小管中的保留晶体转化为混凝土结石。骨桥蛋白(OPN)是肾脏含钙结石基质的主要成分。在本研究中,我们利用OPN基因敲除小鼠来评估OPN在草酸钙晶体早期形态变化中的作用:野生型小鼠(WT)和OPN基因敲除小鼠(KO)腹内注射100 mg/kg乙醛酸盐一周,24小时尿草酸排泄量在野生型和KO小鼠之间没有显著差异。Pizzolato染色可明显检测到肾脏晶体沉积,von Kossa染色未检测到,且KO组明显少于WT组。偏光光学显微镜和扫描电子显微镜的形态观察显示,WT组大鼠肾小管内有大的花状晶体生长,KO组小而均匀的晶体生长。X-射线衍射检测到两种基因型的晶体成分均为一水合草酸钙。OPN免疫组织化学染色显示WT晶体含有OPN蛋白,而不含KO晶体。我们得出结论,OPN在小鼠肾脏草酸钙晶体向结石的形态转化过程中起着至关重要的作用。
An important process in kidney stone formation is the conversion of retentive crystals in renal tubules to concrete stones. Osteopontin (OPN) is the major component of the kidney calcium-containing stone matrix. In this study, we estimated OPN function in early morphological changes of calcium oxalate crystals using OPN knockout mice: 100 mg/kg glyoxylate was intra-abdominally injected into wildtype mice (WT) and OPN knockout mice (KO) for a week, and 24-h urine oxalate excretion showed no significant difference between WT and KO. Kidney crystal depositions were clearly detected by Pizzolato staining but not by von Kossa staining in both genotypes, and the number of crystals in KO was significantly fewer than in WT. Morpholooical observation by polarized light optical microphotography and scanning electron microphotography (SEM) showed large flower-shaped crystals growing in renal tubules in WT and small and uniform crystals in KO. X-ray diffraction detected the crystal components as calcium oxalate monohydrate in both Genotypes. Immunohistochemical staining of OPN showed that the WT crystals contained OPN protein but not KO crystals. We concluded that OPN plays a crucial role in the morphological conversion of calcium oxalate crystals to stones in mouse kidneys.