Table 1.
Biomarkers in EV-derived from the serum/SF of patients with joint arthritis.
| EV-derived biomarkers | EV Source | Expression levels | Possible biological effects/reasons | Source of OA joints | Reference |
|---|---|---|---|---|---|
| microRNAs (miR) | |||||
| miR-126-3p | Human synovial fluid | Downregulation in OA patients | In vivo, rat SFC-derived EVs containing miR-126-3p could constrain chondrocyte inflammation and cartilage degeneration | SF from knees of OA patients undergoing TKR | 73 |
| miR-500b miR-720 miR-4454 miR-199b-5p miR-3154 |
Human synovial fibroblasts | Upregulation with IL-1β stimulation | All of them presented in IL-1β-stimulated SFB and EVs from IL-1β-stimulated SFB | Normal human knee synovial fibroblasts and chondrocytes | 111 |
| miR-504-3p miR-16-2-3p miR-210-5p miR-26a-5p miR-146a-5p miR-6821-5p miR-68678-3p |
Human synovial fluid | Upregulation Upregulation Upregulation Downregulation Downregulation Downregulation Downregulation |
miR-504-3p is the only common miR upregulated in both male and female OA patients, highly gender-specific. | Normal/OA SF was obtained from knee joints of patients undergoing arthrocentesis/ TKR | 112 |
| miR-372-3p | Human chondrocytes | Upregulation in OA chondrocytes | Promoted cell growth and proliferation GSK signalling pathway |
Human cartilage specimens were obtained from patients undergoing TKR | 66 |
| miR-449a-5p | Human primary chondrocytes |
Upregulation with IL-1β treatment | Inhibit ATG4B expression and autophagy in LPS-primed macrophages | Human cartilage specimens were obtained from patients undergoing TKR | 67 |
| miR-155-5p | Human synovial fluid | Upregulation | Potentially stimulate a positive feedback loop of TNF-α stimulated inflammation | SF was obtained from knee joints of patients (ages of 40-60) undergoing arthrocentesis | 113 |
| Long non-coding RNA (lncRNA) | |||||
| PVT1 | Human serum | Upregulation | EV-derived PVT1 regulated OA progression by modulating the HMGB1/Tlr4/NF-κB pathway | Whole blood was extracted from 30 OA patients (ages range from 50-70 years old) and 30 healthy volunteers (ages range from 50-70 years old) | 74 |
| HULC | Human chondrocytes | Downregulation in OA chondrocytes | Suppressed cell growth and proliferation GSK signalling pathway | Human cartilage specimens were obtained from patients undergoing TKR | 66 |
| PCGEM1 | Human synovial fluid | Late-stage OA > early-stage OA > Control | Distinguish the stage of OA. There was a positive relationship between EV-derived lncRNA PCGEM1 and WOMAC Index | Blood sample from the cubital vein and synovial fluid sample from knee joints: (1) 20 healthy people who suffered from incidental knee pain as a control group; (2) 20 patients with primary OA in the early stage; (3) 22 patients with primary OA in the progressive stage (late-stage) | 70 |
| Proteins | |||||
| Haemoglobin Actin-related protein 2/3 complex subunit 3 |
Human synovial fluid | Upregulation | More abundant in OA than those in RA, spondyloarthritis (axSpA), and gout | SF-derived EVs were isolated from RA, axSpA, gout, and OA patients | 75 |
| COL6A1 Β-2glycoprotein I Complement component 5-variant Haptoglobin Alpha-1-acid glycoprotein Ceruloplasmin KIAA1466 CCDC101 PPARBP Apolipoprotein Anti-folate binding protein Anti-HER3 HRV Fab N27-VL C1QC |
Human synovial fluid | Upregulation (Male) Upregulation (Male) Upregulation (Male) Upregulation (Female) Upregulation (Female) Upregulation (Female) Downregulation (Male) Downregulation (Male) Downregulation (Male) Downregulation (Female) Downregulation (Female) Downregulation (Female) Downregulation (Female) Downregulation (Female) |
The upregulated or downregulated markers were gender-dependent in EV protein cargo from SF of non-OA and OA patients | Knee joint synovial fluid from both healthy and osteoarthritic knees was obtained from patients (8 non-OA females, 10 OA females, 7 non-OA male, and 7 OA male patients) undergoing arthrocentesis/total knee arthroplasty procedures. | 114 |
| Toll-like receptor 3 (TLR3) | Human serum | 24- and the 17- to 18-kDA TLR3 showed ~6-fold higher intensity in the active RA group than in the other groups | The increased TLR3 expression in active RA patients might reflect the inflammatory conditions of fibroblast-like synoviocyte | Whole blood was extracted from 33 patients (12 with active RA, 11 with inactive RA, 10 with OA, and 10 healthy donors) | 115 |