PMID- 33759195 OWN - NLM STAT- MEDLINE DCOM- 20211213 LR - 20211214 IS - 1749-6632 (Electronic) IS - 0077-8923 (Linking) VI - 1503 IP - 1 DP - 2021 Nov TI - Extracellular vesicles from M1-polarized macrophages promote inflammation in the temporomandibular joint via miR-1246 activation of the Wnt/beta-catenin pathway. PG - 48-59 LID - 10.1111/nyas.14590 [doi] AB - 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-1beta, 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 GSK3beta and Axin2 and found that miR-1246 inhibits GSK3beta and Axin2 expression, causing activation of the Wnt/beta-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. CI - (c) 2021 New York Academy of Sciences. FAU - Peng, Sisi AU - Peng S AD - College of Stomatology, Chongqing Medical University, Chongqing, China. AD - Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, China. AD - Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. FAU - Yan, Yin AU - Yan Y AD - College of Stomatology, Chongqing Medical University, Chongqing, China. AD - Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, China. AD - Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. FAU - Li, Rui AU - Li R AD - College of Stomatology, Chongqing Medical University, Chongqing, China. AD - Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, China. AD - Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. FAU - Dai, Hongwei AU - Dai H AD - College of Stomatology, Chongqing Medical University, Chongqing, China. AD - Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, China. AD - Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. FAU - Xu, Jie AU - Xu J AD - College of Stomatology, Chongqing Medical University, Chongqing, China. AD - Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing, China. AD - Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210323 PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (MIRN1246 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - Arthritis/*etiology/*metabolism/pathology MH - Biomarkers MH - Cytokines/metabolism MH - Disease Susceptibility MH - Extracellular Vesicles/*metabolism MH - Gene Expression Regulation MH - Humans MH - Inflammation Mediators MH - Macrophage Activation/genetics/immunology MH - Macrophages/immunology/*metabolism MH - MicroRNAs/*genetics MH - Temporomandibular Joint/*pathology MH - *Wnt Signaling Pathway OTO - NOTNLM OT - M1 OT - Wnt/beta-catenin OT - extracellular vesicles OT - inflammation OT - macrophage OT - microRNA OT - temporomandibular joint EDAT- 2021/03/25 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/03/24 07:02 PHST- 2021/02/17 00:00 [revised] PHST- 2020/10/28 00:00 [received] PHST- 2021/02/24 00:00 [accepted] PHST- 2021/03/25 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/03/24 07:02 [entrez] AID - 10.1111/nyas.14590 [doi] PST - ppublish SO - Ann N Y Acad Sci. 2021 Nov;1503(1):48-59. doi: 10.1111/nyas.14590. Epub 2021 Mar 23.