Extracellular vesicles from M1-polarized macrophages promote inflammation in the temporomandibular joint via miR-1246 activation of the Wnt/β-catenin pathway.

Macrophage-mediated regulation of chondrocytes plays an important role in promoting temporomandibular joint (TMJ) inflammation. We investigated whether extracellular vesicles (EVs) derived from M1 macrophages (M1-EVs) have a proinflammatory effect on TMJ inflammation and what the associated mechanisms are. In vitro, purified THP-1 cell-derived M1-EVs were applied to human TMJ condylar chondrocytes, and in vivo M1-EVs derived from bone marrow-derived macrophages (BMDMs) were injected into rat TMJs. The levels of IL-6, IL-8, IL-1β, and matrix metalloproteinase were then evaluated and found to be upregulated in the chondrocytes and rat TMJs. MicroRNA sequencing analysis was performed to identify differential expression of miRNAs, including miR-1246. High expression of miR-1246 in M1-EVs from synovial fluid of patients with TMJ osteoarthritis and synovitis was verified by RT-PCR. We then identified miR-1246 targets GSK3β and Axin2 and found that miR-1246 inhibits GSK3β and Axin2 expression, causing activation of the Wnt/β-catenin pathway and inflammation in condylar chondrocytes. Our study found that M1-EVs promote inflammation by transfer of miR-1246 to condylar chondrocytes, thus providing new insight into one mechanism that can promote TMJ inflammation.