Extracellular Vesicles From M1-polarized Macrophages Are Associated With Inflammation In The Temporomandibular Joint Via The MiR-1246/Wnt/β-catenin Pathway

Temporomandibular joint osteoarthritis(TMJOA)is a common disease characterized by inflammation and cartilage degradation Proinflammatory M1macrophage–mediated regulation of chondrocytes plays an important role in promoting temporomandibular joint(TMJ)inflammation.Our study investigated whether extracellular vesicles(EVs)derived from M1macrophages(M1-EVs)have a proinflammatory effect and what the associated mechanisms are.Here,purified THP-1 cell–derived M0-EVs and M1-EVs were applied to human condylar chondrocytes in vitro.In vivo,bone marrow-derived macrophage(BMDM)-derived M1-EVs were injected into rat TMJs.The levels of IL-6,IL-8,IL-β,and matrix metalloproteinases were upregulated after THP-1 cell-derived M1-EV treatment in TMJ chondrocytes and BMDM-derived M1-EVstreatment in rat TMJs.Micro RNA(miRNA)sequencing analysis was performed to identify the greatest differential expression of miRNAs in THP-1 cell-derived M1-EVs compared with M0-EVs.The high expression of miR-1246 in EVs from synovial fluid of patients with TMJ osteoarthritis and synovitis was verified by RT-PCR.Thus,miR-1246 was selected,and Target Scan、 miRTar Base、miRDB and relevant studise were used to screen for its targets,which are GSK-3β and Axin2.Our results show that miR-1246 inhibits GSK-3β and Axin2 expression,causing activation of the Wnt/β-catenin pathway and inflammation in condylar chondrocytes.In summary,our study suggests that M1-EVs loaded with miR-1246 promote inflammation in condylar chondrocytes and provides new insight into the pathomechanism of TMJ inflammation.