绝经后骨质疏松症患者血浆 miRNA-21 和 miRNA-422a 的上调。
Up-regulation of plasma miRNA-21 and miRNA-422a in postmenopausal osteoporosis.
机构信息
Department of Biochemistry and Dietetics, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
出版信息
PLoS One. 2023 Oct 18;18(10):e0287458. doi: 10.1371/journal.pone.0287458. eCollection 2023.
BACKGROUND
Many researchers focused on diverse miRNAs in the progression of osteoporosis in postmenopausal women. This study aimed to evaluate the association between plasma miRNA-21-5p and miRNA-422a with osteoporosis in postmenopausal women.
METHODS
This cross-sectional comparative study was performed on 126 randomly selected postmenopausal women aged 50-65, including 65 osteoporotic and 61 normal-bone mineral density (BMD) women. miRNA-21 and miRNA-422a were identified using qRT-PCR in these women. BMD was evaluated by the dual-energy X-ray absorptiometry method. A binary logistic regression model adjusted for confounders was used to evaluate the associations between plasma miRNAs' expression levels and osteoporosis. The Area Under Curve (AUC) was calculated to differentiate low BMD in the postmenopausal period using Receiver-Operator Characteristic (ROC) curves.
RESULTS
miRNA-21 and miRNA-422a were significantly up-regulated in osteoporotic compared to non-osteoporotic postmenopausal women. The expression levels of miRNA-21 and miRNA-422a indicated a significant reverse correlation with both lumbar spine and femoral neck density. After adjusting the confounders, the likelihood of osteoporosis in the postmenopausal women with under the median plasma levels of miRNA-21 (OR = 0.025; 95% CI: 0.003 to 0.198, p<0.001) and miRNA-422a (OR = 0.037; 95% CI: 0.007 to 0.211, p<0.001) was significantly less than the women with the levels above the median. There were significant inverse correlations between miRNA-21 (p<0.001, r = -0.511) and miRNA-422a (p<0.001, r = -0.682) with BMD-lumbar spine as well as an inverse correlation between miRNA-21(p<0.001, r = -0.374) and miRNA-422a (p<0.001, r = -0.602) with BMD-femoral neck. The AUC (95%CI) for miRNA-21 and miRNA-422a was 0.84 (0.77 to 0.91) and 0.98 (0.96 to 0.99), respectively. ROC analysis illustrated that sensitivity and specificity values were 83.1% and 74%, respectively, for miRNA-21 at the cut-off point of 3.38. Also, at the cut-off point of 2.86, a sensitivity of 94% as well as a specificity of 89% was determined for miRNA-422a.
CONCLUSIONS
This study indicated that the odds of osteoporosis in postmenopausal women increased with the higher expression of plasma miRNA-21 and miRNA-422a.
背景
许多研究人员专注于绝经后妇女骨质疏松症进展中的不同 miRNAs。本研究旨在评估血浆 miRNA-21-5p 和 miRNA-422a 与绝经后妇女骨质疏松症之间的关联。
方法
本横断面对比研究纳入了 126 名随机选择的 50-65 岁绝经后妇女，包括 65 名骨质疏松症和 61 名正常骨密度（BMD）妇女。使用 qRT-PCR 鉴定这些妇女的 miRNA-21 和 miRNA-422a。使用双能 X 射线吸收法评估 BMD。使用二元逻辑回归模型调整混杂因素，评估血浆 miRNA 表达水平与骨质疏松症之间的关联。使用接收者操作特征（ROC）曲线计算曲线下面积（AUC）以区分绝经后低 BMD。
结果
与非骨质疏松症绝经后妇女相比，骨质疏松症绝经后妇女的 miRNA-21 和 miRNA-422a 表达水平显著上调。miRNA-21 和 miRNA-422a 的表达水平与腰椎和股骨颈密度呈显著负相关。在调整混杂因素后，血浆中 miRNA-21 中位数以下水平的绝经后妇女发生骨质疏松症的可能性（OR = 0.025；95%CI：0.003 至 0.198，p<0.001）和 miRNA-422a（OR = 0.037；95%CI：0.007 至 0.211，p<0.001）显著低于中位数水平的妇女。miRNA-21（p<0.001，r=-0.511）和 miRNA-422a（p<0.001，r=-0.682）与 BMD-腰椎之间存在显著负相关，miRNA-21（p<0.001，r=-0.374）和 miRNA-422a（p<0.001，r=-0.602）与 BMD-股骨颈之间也存在负相关。miRNA-21 和 miRNA-422a 的 AUC（95%CI）分别为 0.84（0.77 至 0.91）和 0.98（0.96 至 0.99）。ROC 分析表明，miRNA-21 在截点为 3.38 时的敏感性和特异性分别为 83.1%和 74%。此外，miRNA-422a 在截点为 2.86 时，敏感性为 94%，特异性为 89%。
结论
本研究表明，绝经后妇女的骨质疏松症风险随着血浆 miRNA-21 和 miRNA-422a 表达水平的升高而增加。
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