The role and mechanism of plasma microRNA-146a in the early diagnosis of osteoarthritis

Abstract

Objective To investigate the difference of microRNA (miRNA, miR)-146a-3p in plasma of patients with different grades of osteoarthritis (OA), and explore its molecular mechanism in the early development of OA. Methods The expression of miR-146a-3p was detected by real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) both in plasma of patients with different grades of OA and OA cell models. The mRNA expression of OA related factors, such as cartilage oligomeric matrix protein (COMP), matrix metalloproteinase-13 (MMP-13), collagen type Ⅱ alpha 1 (COL2A1) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), was detected in human articular chondrocytes after transient transfection of miR-146a-3p mimics/inhibitor. The miR-146a-3p target genes were predicted by bioinformatics methods. Results With the increase of OA grades, the plasma miR-146a-3p content was gradually decreased (F=3.15, P=0.012). The miR-146a-3p level in pre-OA group (4.41±2.55) was between the control group (2.79±1.59) and OA I group (5.52±2.48). The expression of miR-146a-3p in human articular chondrocytes was decreased significantly with the time of IL-1β treatment (F=24.32, P=0.000). After transient transfection of miR-146a-3p mimics/inhibitor, the expression of COMP and MMP-13 gene in human articular chondrocytes changed reversely with miR-146a-3p expression levels. MiRanda database predicts that COMP and MMP-13 may be the target genes of miR-146a-3p. Conclusion MiR-146a-3p is involved in the early development of OA. It may play a biological role by down-regulating MMP-13 and COMP, which provids a new biomarker and therapeutic target for early OA diagnosis and treatment. Key words: Osteoarthritis; MicroRNA-146a-3p; Articular chondrocytes; Cartilage oligomeric matrix protein; Matrix metalloproteinase-13