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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 fluidPlasma: 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]SerumScreening: 5 OA, 5 RA and 6 CTL
Validation: 102 ACL and 60 CTL
41 yrs or youngersone year after anterior cruciate ligament injury
no indication of OA at other sites
Okuhara A, 2012 [15]Peripheral blood mononuclear cells36 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]PlasmaScreening: 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]SerumScreening: 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 fluidScreening: 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 cell100 patients with knee OA and 50 CTLOA: 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]PlasmaScreening: 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]serumScreening: 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, 2010High 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, 2012miRNeasy 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, 2012Trizol 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, 2014Mini 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, 2015Mini 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, 2016miRCURY 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 indicated23a-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, 2017miRVana 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, 2017LeukoLOCK 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, 2017RiboEXTMLS 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