Journal
ADVANCES IN MEDICAL SCIENCES
Volume 65, Issue 1, Pages 78-85Publisher
MEDICAL UNIV BIALYSTOK
DOI: 10.1016/j.advms.2019.12.005
Keywords
miR-146a; Single nucleotide polymorphisms; Interleukins; Metalloproteinases; Osteoarthritis
Categories
Funding
- Research Committee of the University of Thessaly
- European Union (European Social Fund - ESF) through the Operational Program Human Resources Development, Education and Lifelong Learning [MIS-5001552]
Ask authors/readers for more resources
Purpose: MiR-146a acts as a negative inflammatory mediator in different diseases and has been implicated in osteoarthritis (OA) pathogenesis. In our study, we investigated the association between miR-SNP rs2910164 and OA susceptibility and its role on the expression of miR-146a, inflammatory and catabolic mediators in osteoarthritic chondrocytes. Materials and methods: Genetic association analysis was performed in 1688 knee OA patients and healthy individuals of Greek origin. Genomic DNA was extracted from blood and genotyped for rs2910164 (G > C) using Restriction-Fragment Length Polymorphism (RFLP). Total RNA was extracted from chondrocytes of 18 OA patients and miR-146a, IL-1 Receptor-Associated Kinase 1 (IRAK-1), TNF Receptor-Associated Factor 6 (TRAF-6), A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 (ADAMTS-5), Matrix Metalloproteinase-13 (MMP-13), Interleukin-6 (IL-6), Interleukin-1 Beta (IL-1 beta) and Tumor Necrosis Factor-Alpha (TNF-alpha) expression was evaluated using quantitative Real-Time PCR (qRT-PCR). Results: OA patients carrying rs2910164-GC and CC genotypes did not have an increased risk for OA development compared to GG genotype carriers. MiR-146a expression in OA chondrocytes was significantly lower in patients with rs2910164-GC genotype than in the GG carriers. OA patients carrying the rs2910164-GC genotype in their chondrocytes exhibited increased IRAK-1, TRAF-6, MMP-13, IL-1 beta and IL-6 expression levels compared with rs2910164-GG carriers. Conclusion: We demonstrate, for the first time, that miR-SNP rs2910164 in miR-146a gene is associated with reduced miR-146a and increased inflammatory and catabolic mediators' expression in OA chondrocytes. Our data imply that genetic variations in miRNAs linked to OA pathogenesis may regulate their expression levels, suggesting new therapeutic strategies for patients with cartilage diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available