Yavropoulou Maria P, Vaios Vasilios, Makras Polyzois, Georgianos Panagiotis, Batas Anastasios, Tsalikakis Dimitrios, Tzallas Alexandros, Ntritsos Georgios, Roumeliotis Stefanos, Eleftheriadis Theodoros, Liakopoulos Vassilios
Endocrinology Unit, The First Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, GR 11527 Athens, Greece.
Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, GR 11525 Athens, Greece.
Biomedicines. 2020 Dec 12;8(12):601. doi: 10.3390/biomedicines8120601.
The pathophysiology of chronic kidney disease-mineral and bone disorder (CKD-MBD) is complex and multifactorial. Recent studies have identified a link between microRNAs (miRNAs) and bone loss. In this study, we investigated the expression of miRNAs in CKD-MBD. In this case-control study, we included thirty patients with CKD-MBD (cases) and 30 age- and gender-matched healthy individuals (controls). Bone mineral density (BMD) and trabecular bone score (TBS) evaluation was performed with dual X-ray absorptiometry. The selected panel of miRNAs included: hsa-miRNA-21-5p; hsa-miRNA-23a-3p; hsa-miRNA-24-2-5p; hsa-miRNA-26a-5p; hsa-miRNA-29a-3; hsa-miRNA-124-3p; hsa-miRNA-2861. The majority of cases had low BMD values. The relative expression of miRNA-21-5p was 15 times lower [fold regulation (FR): -14.7 ± 8.1, = 0.034), miRNA-124-3p, 6 times lower (FR: -5.9 ± 4, = 0.005), and miRNA-23a-3p, 4 times lower (FR: -3.8 ± 2.0, = 0.036) in cases compared to controls. MiRNA-23a-3p was significantly and inversely correlated with TBS, adjusted for calcium metabolism and BMD values (beta = -0.221, = 0.003, 95% CI -0.360, -0,081) in cases. In a receiver operating characteristic (ROC) analysis, expression of miRNA-124-3p demonstrated 78% sensitivity and 83% specificity in identifying CKD patents with osteoporosis. Serum expression of miRNAs related to osteoblasts (miRNA-23a-3p) and osteoclasts (miRNA-21-5p, miRNA-124-3p) is significantly altered in patients with CKD-MBD.
慢性肾脏病 - 矿物质和骨异常（CKD - MBD）的病理生理学复杂且具有多因素性。最近的研究已经确定了微小RNA（miRNA）与骨质流失之间的联系。在本研究中，我们调查了CKD - MBD中miRNA的表达情况。在这项病例对照研究中，我们纳入了30例CKD - MBD患者（病例组）和30名年龄及性别匹配的健康个体（对照组）。采用双能X线吸收法进行骨密度（BMD）和小梁骨评分（TBS）评估。所选的miRNA panel包括：hsa - miRNA - 21 - 5p；hsa - miRNA - 23a - 3p；hsa - miRNA - 24 - 2 - 5p；hsa - miRNA - 26a - 5p；hsa - miRNA - 29a - 3；hsa - miRNA - 124 - 3p；hsa - miRNA - 2861。大多数病例的BMD值较低。与对照组相比，病例组中miRNA - 21 - 5p的相对表达低15倍[倍数调节（FR）：-14.7±8.1，P = 0.034]，miRNA - 124 - 3p低6倍（FR：-5.9±4，P = 0.005），miRNA - 23a - 3p低4倍（FR：-3.8±2.0，P = 0.036）。在病例组中，经钙代谢和BMD值校正后，miRNA - 23a - 3p与TBS显著负相关（β=-0.221，P = 0.003，95% CI -0.360，-0.081）。在受试者工作特征（ROC）分析中，miRNA - 124 - 3p的表达在识别患有骨质疏松症的CKD患者时显示出78%的敏感性和83%的特异性。在CKD - MBD患者中，与成骨细胞相关的miRNA（miRNA - 23a - 3p）和与破骨细胞相关的miRNA（miRNA - 21 - 5p，miRNA - 124 - 3p）的血清表达显著改变。
