Reversing cortical porosity: Cortical pore infilling in preclinical models of chronic kidney disease.

Reversing cortical porosity: Cortical pore infilling in preclinical models of chronic kidney disease.
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逆转皮质孔隙:慢性肾脏疾病临床前模型中的皮质孔隙填充。

DOI:
10.1016/j.bone.2020.115632
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发表时间:
2021-03
期刊:
影响因子:
4.1
通讯作者:
Allen MR
Allen MR
中科院分区:
医学2区
文献类型:
--
作者:
Metzger CE;Swallow EA;Stacy AJ;Tippen SP;Hammond MA;Chen NX;Moe SM;Allen MR

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慢性肾脏疾病(CKD)患者骨折的发生率很高,部分原因是皮质多孔性。这项研究的目的是利用两种进行性慢性肾脏病的啮齿动物模型来研究皮质毛孔填充。实验一:16周龄雌性C57BI/6J小鼠,饲喂0.2%的腺嘌呤诱导CKD,10周后给予补钙水(1.5%和3%)抑制甲状旁腺激素4周。实验2:雄性Cy/+大鼠至30周龄,用活体μCT评估基线孔隙度。第二次体内扫描是在补充3%Ca-H2O 5周后进行的。实验1:未处理的腺嘌呤小鼠血尿素氮(BUN)、甲状旁腺激素(PTH)和皮质孔隙率(~2.6%孔隙率)增加,而Ca-H2O降低PTH和皮质孔隙率(0.5%-0.8%孔隙率)。实验2:雄性Cy/+大鼠在基础状态下有不同的孔隙率(0.5%-10%),但经Ca-H2O抑制甲状旁腺素后,所有大鼠的皮质孔隙率均低于0.5%。通过定制的MatLab代码测量的单个孔动力学显示,85%的孔被填充,而12%的孔大小收缩。补充Ca-H2O会随着时间的推移导致皮质毛孔的净填充,并赋予机械方面的好处。虽然补钙治疗慢性肾脏病不是一种可行的临床治疗方法,但这些数据表明毛孔填充是可能的,需要进一步的研究来检查可能导致慢性肾脏病净毛孔填充的临床相关治疗方法。
Chronic kidney disease (CKD) patients have a high incidence of fracture due in part to cortical porosity. The goal of this study was to study cortical pore infilling utilizing two rodent models of progressive CKD. Exp 1: Female C57BI/6J mice (16-week-old) were given dietary adenine (0.2%) to induce CKD for 10 weeks after which calcium water supplementation (Ca-H2O; 1.5% and 3%) was given to suppress PTH for another 4 weeks. Exp 2: Male Cy/+ rats were aged to ~30 weeks with baseline porosity assessed using in vivo μCT. A second in vivo scan followed 5-weeks of Ca-H2O (3%) supplementation. Exp 1: Untreated adenine mice had elevated blood urea nitrogen (BUN), parathyroid hormone (PTH), and cortical porosity (~2.6% porosity) while Ca-H2O lowered PTH and cortical porosity (0.5-0.8% porosity). Exp 2: Male Cy/+ rats at baseline had variable porosity (0.5% - 10%), but after PTH suppression via Ca-H2O, cortical porosity in all rats was lower than 0.5%. Individual pore dynamics measured via a custom MATLAB code demonstrated that 85% of pores infilled while 12% contracted in size. Ca-H2O supplementation causes net cortical pore infilling over time and imparted mechanical benefits. While calcium supplementation is not a viable clinical treatment for CKD, these data demonstrate pore infilling is possible and further research is required to examine clinically relevant therapeutics that may cause net pore infilling in CKD.
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DOI: 10.1007/s00223-019-00642-w
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作者:
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