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

Abstract 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.