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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

From: Association of circulating microRNAs with prevalent and incident knee osteoarthritis in women: the OFELY study

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

  1. CTL control, OA osteoarthritis, yrs years, BMI Body Mass Index, KL Kellgren et Lawrence, ACR American College of Rheumatology, Preamp preamplification