Strain-specific alterations in the skeletal response to adenine-induced chronic kidney disease are associated with differences in parathyroid hormone levels.
Strain-specific alterations in the skeletal response to adenine-induced chronic kidney disease are associated with differences in parathyroid hormone levels.
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DOI：
10.1016/j.bone.2021.115963
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发表时间：
2021-07
期刊：
影响因子：
4.1
通讯作者：
Allen MR
中科院分区：
文献类型：
--
作者：
Metzger CE;Swallow EA;Stacy AJ;Allen MR
慢性肾脏疾病（CKD）通过皮质变薄和皮质多孔性的发展导致皮质骨丢失。本研究的目的是评估皮质骨改变腺嘌呤诱导的慢性肾病（CKD）在两个品系的小鼠与已知的遗传差异，在皮质厚度。我们假设，与B6动物相比，具有较厚皮质和皮质内重塑基线水平的C3 H小鼠对腺嘌呤诱导的CKD的反应具有更大的皮质孔隙率。对16周龄的雌性C57 BL/6 J（B6）和C3 H/Hej（C3 H）给予含0.2%腺嘌呤的饮食以诱导CKD 6周，然后给予对照饮食4周。年龄和品系匹配的对照组喂食不含腺嘌呤的对照饮食10周（每组每品系n=8）。与品系匹配的对照组相比，两种腺嘌呤喂养的小鼠品系的血尿素氮均升高，表明肾功能受损，但与B6对照组相比，仅B6腺嘌呤小鼠具有统计学上更高的甲状旁腺激素（PTH）、更大的皮质孔隙率、高骨转换率、更大的RANKL和IL-17阳性骨细胞百分比以及更低的骨细胞凋亡。C3 H小鼠在对照组和腺嘌呤组小鼠中均存在皮质内重塑，而B6小鼠仅在腺嘌呤组小鼠中存在皮质内重塑。与对照组相比，两种品系的腺嘌呤小鼠的皮质厚度较低，TNF-α阳性骨细胞百分比较高。虽然两种品系的小鼠都有肾脏疾病的生化标志物，但只有B6小鼠出现了PTH显著升高、骨转换率高和皮质孔隙发育的表型。这项工作，在进行性CKD的模型中，进一步证实了慢性升高的PTH在皮质多孔性发展中的作用，并证明腺嘌呤诱导的PTH增加有助于B6小鼠的皮质内重塑。腺嘌呤诱导的变化发生在两个品系的小鼠中，显著降低皮质厚度和表达TNF-α的骨细胞百分比较高，表明对CKD的潜在PTH非依赖性反应。
Chronic kidney disease (CKD) leads to loss of cortical bone through cortical thinning and the development of cortical porosity. The goal of this current study was to assess cortical bone alterations to adenine-induced chronic kidney disease (CKD) in two strains of mice with known genetic differences in cortical thickness. We hypothesized that C3H mice with thicker cortices and baseline levels of intracortical remodeling would have greater cortical porosity in response to adenine-induced CKD compared to B6 animals. Female C57BL/6J (B6) and C3H/Hej (C3H) at 16-weeks of age were given a diet with 0.2% adenine to induce CKD for 6 weeks followed by a control diet for 4 weeks. Age- and strain-matched controls were fed the control diet without adenine for the 10-week period (n=8 per group per strain). Both strains of adenine-fed mice had elevated blood urea nitrogen, demonstrating compromised kidney function, compared to strain-matched controls, but only B6 adenine mice had statistically higher parathyroid hormone (PTH), greater cortical porosity, high bone turnover rate, a greater percentage of osteocytes positive for RANKL and IL-17, and lower osteocyte apoptosis compared to B6 controls. C3H mice had intracortical remodeling present in both control and adenine mice, while B6 mice had intracortical remodeling present only in adenine mice. Adenine mice of both strains had lower cortical thickness and a higher percentage of osteocytes positive for TNF-α compared to controls. While both strains of mice had biochemical markers of kidney disease, only B6 mice developed a phenotype with significantly elevated PTH, high bone turnover, and cortical porosity development. This work, in a model of progressive CKD, further confirms the role of chronically elevated PTH in the development of cortical porosity and demonstrates adenine-induced increases in PTH contribute to intracortical remodeling in B6 mice. Adenine-induced changes that occurred in both strains of mice, notably lower cortical thickness and a higher percentage of osteocytes expressing TNF-α, indicate potential PTH-independent responses to CKD.
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影响因子：
4.2
作者：
Metzger, Corinne E.;Swallow, Elizabeth A.;Allen, Matthew R.
通讯作者：
Allen, Matthew R.
影响因子：
19.6
作者：
Menon, V;Greene, T;Sarnak, MJ
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Sarnak, MJ
影响因子：
13.2
作者：
Menon, V;Wang, XL;Sarnak, MJ
通讯作者：
Sarnak, MJ
影响因子：
3.7
作者：
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通讯作者：
Judex S
影响因子：
6.2
作者：
Malluche, Hartmut H.;Mawad, Hanna W.;Monier-Faugere, Marie-Claude
通讯作者：
Monier-Faugere, Marie-Claude