Novel Biomaterial-Based Synovial Fluid Analysis Reveals Protective microRNA Signatures in a Mouse Model of Acute Synovitis-Driven Osteoarthritis

ObjectiveSynovial fluid micro-RNAs have been investigated to clarify the Osteoarthritis (OA) development, however, analyzing them in the murine models had not been established. The purpose of this study was to develop a novel biomaterial-based method to collect murine synovial fluid and elucidate onset mechanism of OA with acute synovitis and continuous mechanical stress. MethodTwelve-week-old C57BL/6J males (n = 72) were divided to the ACL-Transection (ACL-T), ACL-rupture (ACL-R), and Intact groups. We performed joint instability test and histological analysis for cartilage degeneration and synovitis at 2, 6, and 10 weeks. Real time PCR was conducted for articular cartilage at 2 weeks and synovium at 2, 6, and 10 weeks. Tetra-slime was injected into the knee joint and solidified slime including synovial fluid was analyzed in digital PCR at 2 weeks. ResultsAlthough no difference was observed in joint instability between both ACL injury models, acute synovitis and cartilage degeneration were induced in the ACL-T group at 2 weeks. The ACL-T group also increased Mmp-3, Tnf-, Ifn-{gamma}, and inos in synovium, and miR145-5p and miR149-5p in synovial fluid compared to the ACL-R group. However, no histological and biological differences were observed at 6 and 10 weeks. ConclusionAcute synovitis caused secondary cartilage degeneration through MMP-3, TNF-, and M1 macrophage activation in the synovium during the early stage, whereas synovial fluid miR145-5p and miR149-5p were produced to prevent the progression. However, mechanical stress had a much greater impact on cartilage degeneration in the long run rather than synovitis.