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Osteoarthritis Cartilage. 2016 Sep;24(9):1577-86. doi: 10.1016/j.joca.2016.04.019. Epub 2016 Apr 30.

Identification of synovial fluid microRNA signature in knee osteoarthritis: differentiating early- and late-stage knee osteoarthritis.

Author information

The Arthritis Program and Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Princess Margaret Cancer Centre and Department of Computer Science, University of Toronto, Ontario, Canada.
Division of Orthopedics, Toronto Western Hospital, Toronto, Ontario, Canada.
The Arthritis Program and Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Surgery, University of Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. Electronic address:



This study aimed to identify circulating microRNA (miRNA) signatures in knee synovial fluid (SF) from early-stage and late-stage knee osteoarthritis (OA) patients.


miRNAs were screened by miRNA-PCR-arrays and validated by Real-time quantitative polymerase chain reaction (RT-qPCR) in SF from early-stage (Kellgren-Lawrence (KL): Grade: I/II) and late-stage OA patients (Grade: III/IV). OA cartilage or synovial explants were cultured to study the source/release of identified miRNAs. Computational-approach was utilized to predict gene/pathway targets.


Our screening/validation analysis identified a panel of seven (out of 752) circulating miRNAs (23a-3p, 24-3p, 27a-3p, 27b-3p, 29c-3p, 34a-5p and 186-5p) that were significantly differentially expressed in late-stage vs early-stage OA-SF, irrespective of age, gender and Body Mass Index (BMI). miR-378a-5p was mostly detectable in majority of late-stage OA-SF. Cartilage explants stimulated with IL-1β showed a significant reduction in miR-23a-3p, 27a-3p and 27b-3p expression with no significant changes in other validated miRNAs. However, IL-1β-stimulated OA synovial explants exhibited significantly increased expression of miR-23a-3p, 24-3p, 27a-3p, 27b-3p, 29c-3p, 186-5p and 378a-5p, and release of only 23a-3p and 27b-3p in supernatants, suggesting that IL-1β contributes to the release of 23a-3p and 27b-3p into the SF from synovium. Computational-analysis identified 2 genes (ROQUIN-1 [RC3H1] and quaking-gene [QKI]) that are targeted by six out of eight miRNAs; miR-27b-3p exhibited greatest association with RC3H1 and QKI genes. Indeed, synovial explants treated with miR-27b-3p-mimic show significant suppression of both RC3H1 and QKI genes.


We provide first evidence of the differential expression of circulating miRNAs in early-stage vs late-stage knee OA-SF. Further, we provide source, release and genes/pathways regulated by identified miRNAs.


Articular cartilage; Biomarker; Osteoarthritis; Synovial fluid; Synovium; miRNA

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