Table 2.
A summary of studies on human miRNAs with dysregulated expression in patients suffering from OA, including the biological fluid tested, the number of patients with their baseline characteristics, the criteria for patient selection, the quantification methods, and the miRNAs significantly dysregulated
| Murata K, 2010 [13] | Plasma and synovial fluid |
Plasma: 30 knee OA, 30 RA, 30 CTL Synovial fluid: 30 OA, 30 RA |
Plasma: OA: 75,1 yrs, 77 % ; RA: 60.1 yrs, 73%; CTL: 46,5 yrs, 57 % Synovial fluid: RA: 63,1, 80%; OA: 75,3, 80% |
RA and knee OA were diagnosed according to the ACR criteria no indication of OA at other sites |
|
| Zhang L, 2012 [14] | Serum |
Screening: 5 OA, 5 RA and 6 CTL Validation: 102 ACL and 60 CTL |
41 yrs or youngers |
one year after anterior cruciate ligament injury no indication of OA at other sites |
|
| Okuhara A, 2012 [15] | Peripheral blood mononuclear cells |
36 OA 36 CTL |
OA: 68 yrs, 81 % CTL: 32 yrs, 47 % |
Knee OA ACR criteria no indication of OA at other sites |
|
| Borgonio-Cuadra VM, 2014 [16] | Plasma |
Screening: 14 OA and 5 CTL Validation: 27 OA and 27 CTL |
Screening: OA: 55.7 yrs, 71.4 % CTL: 47.5 yrs, 100% Validation: OA: 55.6 yrs, 88.9% CTL: 52.9 yrs, 81.5% |
Knee OA, KL 2/3 and BMI < 27 no indication of OA at other sites |
|
| Beyer C, 2015 [17] | Serum |
Screening: pooled serum from 13 individuals with knee/hip arthroplasty Pooled serum from 13 individuals without knee/hip arthroplasty Validation: 749 OA and 67 CTL |
OA: 65 yrs, 58.2%CTL: 62.7 yrs, 49.3% |
Knee/hip arthroplasty (KL 3,4) no indication of OA at other sites |
|
| Li YH, 2016 [18] | Synovial fluid |
Screening: 4 early OA and 4 late OA Validation: 22 early OA and 26 late OA |
Screening: Early OA: 51 yrs, 100 % Late OA: 64 yrs, 100% Validation: Early OA: 56 yrs, 36.4% Late OA: 60 yrs, 61.5% |
Early stage OA: degenerative meniscal tears undergoing arthroscopic surgery (KL grade 1,2) Late stage OA: total knee replacement surgery (KL grade 3,4) no indication of OA at other sites |
|
| Soyocak A, 2017 [19] | Peripheral blood mononuclear cell | 100 patients with knee OA and 50 CTL |
OA: from 47 to 70yrs, 84% CTL: from 35 to 38 yrs, 84% |
Knee OA, ACR criteria no indication of OA at other sites |
|
| Kong R, 2017 [20] | Plasma |
Screening: 8 knee OA and 8 CTL Validation: 100 OA and 100 CTL |
Screening: OA: 51.13 yrs, 62.5% CTL: 50.75 yrs, 62.5% Validation: OA: 51.69 yrs, 69% CTL: 51.09 yrs, 61% |
Knee OA, ACR criteria no indication of OA at other sites |
|
| Ntoumou E, 2017 [21] | serum |
Screening: 12 primary OA and 12 CTL Validation: 12 OA and 12 CTL |
Screening: OA: 69,8 yrs, 75% CTL: 64,2 yrs, 50% Validation: not indicated |
Knee OA, KL ≥3 no indication of OA at other sites |
|
| Murata, 2010 | High pure miRNA Isolation kit (Roche) | Ncode VILO miRNA cDNA Synthesis kit (Invitrogen) |
Express SYBR GreeER qPCR Supermix (Invitrogen) control: cel-miR-39 |
Applied Biosystems 7300 SDS Relative Quantification 1.3 (Applied Biosystems) |
Plasma miRNAs had distinct pattern from SF miRNAs miR-132: potential diagnostic marker for patients with OA or RA |
| Zhang, 2012 | miRNeasy kit (Quiagen) | Validation: TaqMan miRNA reverse transcription kit (Invitrogen) + a pulsed RT reaction with a Eppendorf mastercycler (Eppendorf) |
Screening: Megaplex RT human pool A and B (Applied) Validation: Preamp, TaqMan PreAmp master mix; qPCR, TaqMan qPCR assays control: U6 (Applied) |
Screening: 7900HT (Applied) Validation: 7500 (Applied) SDS Relative Quantification 2.2.3 (Applied) |
U38 and U48 upregulated in patients developing cartilage damage at one year after ACL injury |
| Okuhara, 2012 | Trizol reagent (Invitrogen) | Thermocycler (BioRad) |
TaqMan miRNA assay kit (Applied) control: U18 |
Mini Opticon Real-time PCR System (BioRad) |
146, 155, 181a, 223 upregulated in OA vs CTL ealy stage: 146a and 223 higher than in late stage |
| Borgonio-Cuadra, 2014 | Mini miRNeasy kit (Quiagen) | Screening: RT Megaplex Pool A on a GeneAmp PCR 9700 System (Applied) Validation: specific miRNA primer and TaqMan probes (Applied) |
Screening: preamp with Megaplex PreAmp MasterMix, TLDA ver.2.0 plate A (Applied) Validation: : preamp with Megaplex PreAmp MasterMix, qPCR control: U6 |
Screening and Validation: : 7900HT (Applied) | 12 miRNAs overexpressed in OA vs CTL: 16, 20b, 29c, 30b, 93, 126, 146a, 184, 186, 195, 345, 885-5p |
| Beyer, 2015 | Mini miRNeasy kit (Quiagen) | Megaplex Primer Pools (Human Pools A V.2.1) (Applied) |
Screening: Human TaqMan miRNA Array Card A V.2.1 (Applied) Validation: TaqMan miRNA assays (Applied) control: U6 or Ct average of all miRNA measurements for each sample |
Screening and validation: 7900HT (Applied) SDS 2.2 software (Applied) and LinRegPCR software |
let-7e, 454, 885-5p potential predictors for severe knee or hip OA |
| Li YH, 2016 | miRCURY RNA isolation kit-biofluids (EXIQON) | Universal cDNA synthesis kit II (EXIQON) | miRNA ready-to-use PCR array (Human panel I + II, EXIQON) using ExiLENT SYBR Green master mix (EXIQON) | not indicated |
23a-3p, 24-3p, 27b-3p, 29c-3p, 34a-5p, 186-5p upregulated and 27a-5p, 329, 655, 708-3p, 934 downregulated in late stage OA ve early OA 27a-3p, 101-5p, 378-5p only expressed in late stage |
| Soyocak A, 2017 | miRVana miRNA Isolation kit (Applied) | TaqMan MicroRNA Reverse transcription Kit (Applied) |
TaqMan Small RNA Assays, TaqMan Gene Expression Master Mix control: U44 and 18S |
qPCR system (Mx3000p, Stratagene) |
miR-155: increased in OA miR-146a and miR-155 increased in the progressive stages |
| Kong R, 2017 | LeukoLOCK kit (Ambion) |
Screening: microarray hybridation with the GeneChip miRNA 4.0 Array (Affymetrix) Validation: TaqMan microRNA Reverse Transcription kit (Life Technologies) |
Validation: TaqMan miRNA assays (Applied) control: U6 |
7900HT (Applied) |
19b-3p, 92a-3p, 122-5p, 486-5p, 320b increased in OA 19b-3p, 122-5p, 486-5p, great diagnostic value 19b-3p and 486-5p positively corretated with disease severity |
| Ntoumou E, 2017 | RiboEXTMLS kit (Geneall) |
Screening: miRNA complete labeling and hybridization kit (Agilent) using SurePrint G3 Human miRNA 8X60K platform (Agilent) Validation: miScript II Reverse Transcription Kit (QIAGEN) |
Validation: quantification with miScript SYBR Green PCR kit and miScript Primer Assays (QIAGEN) Control: Hsa-miR-25-1 |
Screening: Agilent Feature Extraction Software version 4.0.1.21 Validation: ABI 7300 Real-time PCR system (Applied) |
3 miRNAs significantly downregulated in OA patients: hsa-miR-140-3p, hsa-miR-33b-3p, hsa-miR-671-3p |
CTL control, OA osteoarthritis, yrs years, BMI Body Mass Index, KL Kellgren et Lawrence, ACR American College of Rheumatology, Preamp preamplification