miR ‐34a carried by adipocyte exosomes inhibits the polarization of M1 macrophages in mouse osteolysis model
| Autor: | Wang-chen Zhou, De-qin Geng, Jian Ge, Weiyi Li, Lei Xu, Xuren Gao |
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| Rok vydání: | 2020 |
| Předmět: |
Materials science
Osteolysis 0206 medical engineering Biomedical Engineering Macrophage polarization 02 engineering and technology Exosomes Biomaterials Mice chemistry.chemical_compound Downregulation and upregulation Adipocyte NLR Family Pyrin Domain-Containing 3 Protein Adipocytes medicine Animals Titanium Gene knockdown Macrophages Metals and Alloys Cell Polarity 3T3 Cells Genetic Therapy Transfection Bone prosthesis 021001 nanoscience & nanotechnology medicine.disease 020601 biomedical engineering Up-Regulation MicroRNAs RAW 264.7 Cells chemistry Cell culture Ceramics and Composites Cancer research Nanoparticles 0210 nano-technology |
| Zdroj: | Journal of Biomedical Materials Research Part A. 109:994-1003 |
| ISSN: | 1552-4965 1549-3296 |
| Popis: | Objective After bone prosthesis replacement, M1-type macrophage polarization can be induced by titanium (Ti) particles and produce inflammatory, leading to osteolysis. Adipocyte-derived exosomes (ADEs) exert immune-modulatory impact on the macrophage, while whether it can inhibit the macrophage polarization induced by Ti is unclear. This study focuses on the M1-type macrophage and aims to determine the effect of ADEs on Ti-induced M1-type macrophage polarization in osteolytic mice and the involved mechanism. Methods Ti particle-induced osteolysis mouse model was established and macrophages were isolated from the osteolysis site. The levels of NLRP3 and specific markers for M1-type macrophage were determined. ADEs isolated from adipocyte cell line 3T3-L1, or conditioned ADEs with low-expressed miR-34a isolated from 3T3-L1 transfected with miR-34a inhibitor were co-cultured with RAW 264.7 to determine their impact on the polarization of macrophage. Results ADEs reduced the M1-type macrophage polarization and caused the upregulation of miR-34a in macrophage of the osteolysis site of the osteolysis mouse model. Also, the level of miR-34a in ADEs was higher than that in the adipocyte. The conditioned ADEs expressed a low level of miR-34a and boosted the Ti-induced M1-type polarization. MiR-34a could target NLRP3 and negatively regulated its expression. Moreover, NLRP3 knockdown in macrophage restricted the conditioned ADEs to promote macrophage towards to Ti-induced M1-type polarization. The inhibitory function of ADEs on M1-type macrophage polarization was abolished by miR-34a silencing in the mouse osteolysis model. Conclusion The miR-34a carried by ADEs reduced the polarization of M1-type macrophages by targeting macrophage NLRP3 during Ti particle-induced osteolysis. |
| Databáze: | OpenAIRE |
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