Exploration of miRNA Involved in the Expression of MMP-1 in the Synovium of Osteoarthritic Knee Joints

Abstract

Osteoarthritis (OA) is a joint disease characterized by gradual loss of cartilage matrix. Recently, the increased production of MMP-1, MMP-2 and MMP-3 in synovial tissue (ST) has been considered to be involved in the loss of cartilage in OA. The pathological roles of miRNAs in various diseases have been recently highlighted. We first explored which miRNAs regulate the expression of MMP-1 and then investigated the relationship between the selected miRNAs and MMP-2/MMP-3 in OA synovium. Twenty-six synovial fluid (SF) samples were collected from 26 early- or middle-stage OA knees. In addition, 30 ST samples were prepared from 30 end-stage OA knees during prosthetic replacement arthroplasty. The concentrations of MMPs and amounts of 65 miRNAs in the SF samples were quantified by a Luminex assay and quantitative polymerase chain reaction (qPCR), respectively. The expression of MMPs and miRNAs in the ST samples were quantified by qPCR. As a result, among the 65 miRNAs, miR-21-5p and miR-195 showed a wide range of measurements that were negatively correlated with the measurements of MMP-1 in the SF samples. In the expression analysis of miR-21-5p, miR-195, and MMP1 mRNA in the ST samples, the amount of miR-21-5p but not miR-195 showed a negative correlation with the levels of MMP1 mRNA. We then investigated the relationships between miR-21-5p and MMP-2/MMP-3. As a result, the amounts of miR-21-5p were negatively correlated with the concentration of MMP-2 and MMP-3, respectively, in the SF samples. Similarly, the amounts of miR-21-5p were negatively correlated with the expression of MMP2 and MMP3 mRNA, respectively, in the ST samples. Given these data, we concluded that miR-21-5p may play a role in the increased expression of MMPs in OA synovium.