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.

中文翻译：

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M1极化巨噬细胞的细胞外囊泡通过miR-1246激活Wnt/β-catenin通路促进颞下颌关节炎症

巨噬细胞介导的软骨细胞调节在促进颞下颌关节 (TMJ) 炎症中起重要作用。我们研究了源自 M1 巨噬细胞 (M1-EV) 的细胞外囊泡 (EV) 是否对 TMJ 炎症具有促炎作用以及相关机制是什么。 在体外，纯化的 THP-1 细胞衍生的 M1-EVs 应用于人 TMJ 髁突软骨细胞，并在体内将源自骨髓源性巨噬细胞 (BMDM) 的 M1-EV 注射到大鼠 TMJ 中。然后评估 IL-6、IL-8、IL-1β 和基质金属蛋白酶的水平，发现软骨细胞和大鼠 TMJ 中的水平上调。进行微RNA测序分析以鉴定miRNA的差异表达，包括miR-1246。RT-PCR证实了来自TMJ骨关节炎和滑膜炎患者滑液的M1-EVs中miR-1246的高表达。然后我们确定了 miR-1246 靶向 GSK3β 和 Axin2，发现 miR-1246 抑制 GSK3β 和 Axin2 表达，导致 Wnt/β-catenin 通路的激活和髁突软骨细胞的炎症。我们的研究发现，M1-EVs 通过将 miR-1246 转移到髁突软骨细胞来促进炎症，从而为促进 TMJ 炎症的一种机制提供了新的见解。