Expression of Circulating MicroRNAs Linked to Bone Metabolism in Chronic Kidney Disease-Mineral and Bone Disorder
Maria P Yavropoulou1,2, Vasilios Vaios3, Polyzois Makras2
1Endocrinology Unit, The First Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, GR 11527 Athens, Greece.
Abstract:
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, p = 0.034), miRNA-124-3p, 6 times lower (FR: -5.9 ± 4, p = 0.005), and miRNA-23a-3p, 4 times lower (FR: -3.8 ± 2.0, p = 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, p = 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.
Insights
MicroRNAs (miRNAs) are linked to bone loss in chronic kidney disease-mineral and bone disorder (CKD-MBD). This study found significantly lower levels of specific miRNAs in CKD-MBD patients, suggesting their role in the condition.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Chronic kidney disease-mineral and bone disorder (CKD-MBD) involves complex pathophysiology.
- Emerging research highlights a connection between microRNAs (miRNAs) and bone metabolism.
- Understanding miRNA expression in CKD-MBD is crucial for elucidating bone loss mechanisms.
Purpose of the Study:
- To investigate the expression profiles of specific miRNAs in patients with CKD-MBD.
- To explore the relationship between miRNA expression, bone mineral density (BMD), and trabecular bone score (TBS).
- To assess the diagnostic potential of miRNAs in identifying CKD-MBD-related osteoporosis.
Main Methods:
- A case-control study involving 30 CKD-MBD patients and 30 healthy controls.
- Bone mineral density (BMD) and trabecular bone score (TBS) assessed via dual X-ray absorptiometry.
- Quantitative analysis of selected miRNAs (hsa-miRNA-21-5p, hsa-miRNA-23a-3p, hsa-miRNA-124-3p, etc.) using RT-qPCR.
Main Results:
- CKD-MBD patients exhibited significantly lower BMD compared to controls.
- Reduced expression of miRNA-21-5p (15-fold), miRNA-124-3p (6-fold), and miRNA-23a-3p (4-fold) was observed in CKD-MBD patients.
- MiRNA-23a-3p inversely correlated with TBS, and miRNA-124-3p showed high sensitivity and specificity for detecting osteoporosis in CKD patients.
Conclusions:
- Serum miRNA expression, particularly involving osteoblast- and osteoclast-related miRNAs, is significantly altered in CKD-MBD.
- Specific miRNAs (miRNA-21-5p, miRNA-124-3p, miRNA-23a-3p) are potential biomarkers for bone loss in CKD-MBD.
- MiRNA-124-3p may serve as a valuable diagnostic marker for identifying osteoporosis in CKD patients.
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