Table 3.
Circulating miRNAs related to osteoarthritis (OA).
| Study Population | Variables in Pre-Analytical phase: - Sample matrix - Centrifugation conditions - Storage conditions |
Quantification Method - Target miRNAs - Analytical method - Applied normalization strategy |
- Validated miRNAs - AUC; sensitivity; specificity |
Reference | |
|---|---|---|---|---|---|
| Screening | Validation | ||||
| Knee OA (K/L grade 3, n = 11; K/L grade 4, n = 21), RA (n = 30), and HC (n = 30) |
- EDTA-2K-Plasma - 400g, 7 min - −20 °C |
- miR-223, miR-155, miR-146a, miR-132, and miR-16 - RT-qPCR - cel-miR-39 |
- ↓ miR-132 in RA and OA vs. HC; ↓ miR-16 in OA vs. HC - 0.90; 83.8%; 80.7% for RA and 0.91; 84.0%; 81.2% for OA (miR-132) |
[111] | |
| Screening: OA (K/L grade 2, n = 6; K/L grade 3, n = 8) and HC (n = 5) Validation: OA (K/L grade 2, n = 14; K/L grade 3, n = 13) and HC (n = 27) |
- EDTA-Plasma - (i) 10 min, 1800 g, RT; (ii) 5 min, 15,000g - −80 °C |
- 380 miRNAs - TaqMan Low Density Array ver. 2.0 plate A - MammU6 |
- miR-885-5p, miR-345, miR-195, miR-186, miR-184, miR-146a, miR-126, and miR-93, miR-30b, miR-29c, miR-20b, and miR-16 - RT-qPCR - MammU6 |
- ↑ miR-885-5p, miR-345, miR-195, miR-186, miR-184, miR-146a, miR-126, and miR-93 in OA vs. HC - n.d. |
[112] |
| Knee OA (K/L stage 2, n = 22; K/L stage 3, n = 29; K/L stage 4, n = 23) and HC (n = 79) |
- Sodium citrate-Plasma - n.d. - n.d. |
- miR-136 - RT-qPCR - snRNA U6 |
- ↓ miR-136 in OA K/L grade 2+3+4 vs. HC - ↓ miR-136 in OA K/L grade 4 vs. grade 2 and 3 - ↓ miR-136 in OA K/L grade 3 vs. grade 2 and ↑ vs. grade 4 - ↑ miR-136 in OA K/L grade 2 vs. grade 3 and 4 - 0.94 (miR-136) for OA K/L grade 2+3+4 vs. HC |
[113] | |
| Screening: 13 pooled samples for each group of the entire study population [OA with (K/L grade 3/4, n = 67) and without knee/hip arthroplasty (n = 749)] Validation: OA with (K/L grade 3/4, n = 67) and without knee/hip arthroplasty (n = 749)] |
- Serum - n.d. - n.d. |
- 374 miRNAs - Human TaqMan miRNA array (Card A V.2.1) - snRNA U6 and miR-45 |
- let-7b, let-7e, miR-885-5p, miR-454, miR-342-3p, miR-191, miR-146b, miR-140, miR-122, miR-93, miR-28-3p, and miR-25 - RT-qPCR - Ct average or snRNA U6 |
- ↓ let-7e in severe OA with knee/hip arthroplasty vs. OA without knee/hip arthroplasty - n.d. |
[114] |
| Screening: 8 pooled samples for each group of the entire study population [Knee OA (n = 100) and matched HC (n = 100)] Validation: Knee OA (n = 100) and matched HC (n = 100) |
- Sodium citrate-Plasma, left for 3 h at −4 °C - 10 min, 1500g, RT - −70 °C |
- 2578 miRNAs, 2025 pre-miRNAs - GeneChip miRNA 4.0 Array - The Geoquery package (version 2.34.0) in R language |
- miR-1180-3p, miR-887-5p, miR-663a, miR-486-5p, miR-320b, miR-122-5p, miR-92a-3p, and miR-19b-3p - RT-qPCR - snRNA U6 |
-↑ miR-486-5p (0.89), miR-320b, miR-122-5p (0.63), miR-92a-3p, and miR-19b-3p (0.83) in knee OA vs. HC - 0.93; 80.0%; 88.0% (miR-486-5p+miR-122-5p+miR-19b-3p panel), 0.89 (miR-486-5p), 0.63 (miR-122-5p), 0.83 (miR-19b-3p) for knee OA |
[115] |
| Knee OA (K/L grade 3, n = 4; K/L grade 4, n = 8) and HC (n = 12) undergoing total knee replacement surgery |
- Serum - n.d. - n.d. |
- 2549 miRNAs - Agilent 8×60K miRNA-array platform - Quantile algorithm |
- miR-4284, miR-1233-3p, miR-671-3p, miR-663a, miR-150-5p, miR-140-3p, and miR-33b-3p - RT-qPCR - miR-25-1 |
- ↓ miR-671-3p, miR-140-3p, and miR-33b-3p in OA vs. HC - 0.87 (miR-671-3p), 0.85 (miR-140-3p), 0.81 (miR-33b-3p) |
[116] |
| Screening: PM women with knee OA (K/L grade 2/3, n = 10) and HC (n = 10) Validation: PM women with (i) prevalent knee OA (K/L grade 2/3, n = 43) and age-BMI matched HC (n = 42) (ii) incident knee OA (n = 23) and age-BMI matched HC (n = 25) |
- Serum - n.d. - n.d. |
- miRNA NGS libraries obtained from RNA conversion using NEBNEXT library generation kit - NGS - Values expressed as tags per million |
- miR-1299, miR-885-5p, miR-375, miR-345-5p, miR-200a-3p, miR-199a-3p, miR-195-5p, miR-186-5p, miR-184, miR-146a-5p, miR-139-5p, miR-132-3p, miR-126-3p, miR-93-5p miR-29a-3p, miR-29b-3p, miR-29c-3p, miR-16-5p, and let-7e-5p - RT-qPCR - mean of miR-361-5p, miR-222-3p, and miR-191-5p expression levels |
-↑ miR-146a-5p in prevalent knee OA vs. HC; ↑ miR-186-5p in incident knee OA over the next 4 years - n.d. |
[117] |
| Screening: knee OA who received celecoxib treatment for 6 weeks (K/L grade 2, n = 4; K/L grade 3, n = 2) Validation: knee OA who received celecoxib treatment for 6 weeks (K/L grade 2, n = 159; K/L grade 3, n = 59) |
- Plasma - n.d. - n.d. |
- 2578 miRNAs and 2025 pre-miRNAs - GeneChip miRNA 4.0 Array - Geoquery package (Version 3.3.3) in R language |
- miR-4796, miR-3197, miR-675-3p, miR-320a, miR-210, miR-155-5p, miR-146a-5p, miR-126-5p, miR-92a-3p, and miR-17-3p - RT-qPCR - snRNA U6 |
-↑ miR-320a, miR-126-5p and ↓ miR-155-5p, miR-146a-5p in OA after 6 w of treatment vs. OA before treatment; ↓ miR-320a and ↑ miR-146a-5p, miR-126-5p in non-clinical responders; ↑ miR-320a, miR-126-5p and ↓ miR-146a-5p in clinical responders - n.d. |
[118] |
n.d.: not determined; AUC: Area Under the Curve; HC: Healthy Controls; OA: Osteoarthritis; OP: Osteoporosis; RA: Rheumatoid Arthritis; RT: Room Temperature; RT-qPCR: Real-time quantitative polymerase chain reaction. ↑: increased levels of the validated circulating miRNA; ↓: decreased levels of the validated circulating miRNA.