Expression of bone type 1 PTH receptor in rats with chronic renal failure.
Expression of bone type 1 PTH receptor in rats with chronic renal failure.
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DOI：
10.1007/s10157-006-0455-2
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发表时间：
2007-03-01
影响因子：
2.3
通讯作者：
Sasaki, Sei
中科院分区：
文献类型：
--
作者：
Kuwahara, Michio;Inoshita, Seiji;Sasaki, Sei
一些研究人员推测，骨1型甲状旁腺激素受体（PTH1R）的减少可能是慢性肾衰竭（CRF）中“骨骼抵抗”的原因之一。事实上，PTH1R mRNA的下调已经在尿毒症骨骼中被发现。然而，很少有研究确定PTH1R蛋白的表达模式。在本文中，我们比较了对照和CRF条件下PTH1R蛋白和mRNA的骨表达。Sprague-Dawley大鼠接受5/6肾切除术（Nx）或假手术（对照组），16周后处死。Nx组血尿素氮（BUN）、血清Cr、P和甲状旁腺激素（PTH）均高于对照组，而血清Ca和1,25(OH)(2)D(3)均低于对照组。采用图像处理系统对腰椎标本的免疫组化图像进行分析。PTH1R基本上在所有成骨细胞中都被鉴定出来。根据PTH1R染色的灰度值定量成骨细胞PTH1R蛋白的表达。Nx大鼠成骨细胞平均灰度比对照组低25% (P < 0.01)，而两组间成骨细胞数量和细胞大小无显著差异。因此，可能出现CRF条件下PTH1R蛋白表达下调的情况。从骨样本中提取的总RNA逆转录用于实时聚合酶链反应（PCR）。定量PCR结果显示，Nx组PTH1R mRNA表达量较对照组降低33% （P < 0.05）。我们的研究结果表明，在CRF稳定状态下，成骨细胞PTH1R的蛋白和mRNA水平均下调。
Some researchers have speculated that a decrease in bone type 1 PTH receptor (PTH1R) may be among the causes of "skeletal resistance" in chronic renal failure (CRF). Indeed, the down-regulation of PTH1R mRNA has been identified in uremic bones. However, few studies have identified the patterns of PTH1R protein expression. In this article we compare the bone expression of PTH1R protein and mRNA under control and CRF conditions. Sprague-Dawley rats underwent 5/6 nephrectomies (Nx) or sham operations (control), and were killed 16 weeks later. Blood urea nitrogen (BUN), serum Cr, P, and parathyroid hormone (PTH) were higher in the Nx group than in the controls, while serum Ca and 1,25(OH)(2)D(3) were lower in the Nx group. Immunohistochemical images of lumbar bone samples were analyzed by an image processing system. PTH1R was essentially identified in all osteoblasts. The expression of osteoblast PTH1R protein was quantified based on the gray value of PTH1R staining. The mean gray scale of osteoblasts was 25% lower in Nx rats than in control rats (P < 0.01), whereas osteoblast cell counts and cell sizes were not significantly different between the two groups. Thus, down-regulation of PTH1R protein expression under the CRF condition appeared likely. Total RNA extracted from the bone samples was reverse transcribed for real-time polymerase chain reaction (PCR). PTH1R mRNA expression was 33% lower in the Nx group than in the control group in the quantitative PCR analysis (P < 0.05). Our findings suggested that osteoblast PTH1R expression is down-regulated at both the protein and mRNA levels in the steady state of CRF.