期刊
STEM CELL RESEARCH & THERAPY
卷 10, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13287-019-1341-7
关键词
Osteoarthritis; SHED; Exosomal microRNA; Inflammation; Temporomandibular joint
资金
- National Natural Science Foundation of China [81800999]
- Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN201800414]
- Program for Innovation Team Building at Institutions of Higher Education in Chongqing [CXTDG201602006]
ObjectivesTemporomandibular joint osteoarthritis (TMJOA) is an inflammatory joint disease. This study investigated whether exosomes (Exos) of stem cells from human exfoliated deciduous teeth (SHEDs) have a therapeutic effect on TMJ inflammation and elucidated the underlying mechanisms.Materials and methodsSHEDs were verified by flow cytometry. SHED-Exos were identified by western blotting, nanoparticle tracking analysis, and transmission electron microscopy. Western blot and RT-qPCR were performed to verify the anti-inflammatory effects of SHED-Exos. MicroRNA (miRNA) array analysis was conducted to determine the miRNA expression profiles of SHED-Exos, and the key pathways were analyzed. After chondrocytes were treated with an miR-100-5p mimic or rapamycin, relative expression of genes was measured by RT-qPCR and western blotting. A luciferase reporter assay was performed to reveal the molecular role of the exosomal miR-100 target, mTOR.ResultsMiR-100-5p was enriched in the SHED-Exos. Treatment with SHED-Exos suppressed the expression of interleukin-6 (IL-6), IL-8, matrix metalloproteinase 1 (MMP1), MMP3, MMP9, MMP13, and disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5). Chondrocytes treated with the miR-100 mimic showed lower expression of MMP1, MMP9, MMP13, ADAMTS5, and mTOR. In contrast, miR-100 downregulation upregulated the MMPs and mTOR. Rapamycin treatment upregulated miR-100 and downregulated MMPs and ADAMTS5. Furthermore, the luciferase reporter assay demonstrated that miR-100-5p directly targeted the mTOR 3 untranslated region and that SHED-Exos miR-100-5p repressed mTOR expression.Conclusions This study demonstrated that SHED-Exos suppress inflammation in TMJ chondrocytes and may thus be a novel therapeutic agent for TMJ inflammation.
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