Exosomes derived from synovial fibroblasts from patients with rheumatoid arthritis promote macrophage migration that can be suppressed by miR-124-3p
Objectives: Exosomes are potent vehicles for intercellular communication. Rheumatoid arthritis (RA) is a chronic systemic disease of unknown etiology. Local administration of miR-124 precursor to rats with adjuvant-induced arthritis suppresses systemic arthritis and bone destruction. Thus, exosomes...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402302193X |
| _version_ | 1827957355349803008 |
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| author | Yuji Nakamachi Kenichi Uto Shinya Hayashi Takaichi Okano Akio Morinobu Ryosuke Kuroda Seiji Kawano Jun Saegusa |
| author_facet | Yuji Nakamachi Kenichi Uto Shinya Hayashi Takaichi Okano Akio Morinobu Ryosuke Kuroda Seiji Kawano Jun Saegusa |
| author_sort | Yuji Nakamachi |
| collection | DOAJ |
| description | Objectives: Exosomes are potent vehicles for intercellular communication. Rheumatoid arthritis (RA) is a chronic systemic disease of unknown etiology. Local administration of miR-124 precursor to rats with adjuvant-induced arthritis suppresses systemic arthritis and bone destruction. Thus, exosomes may be involved in this disease. We aimed to determine the role of exosomes in the pathology of RA. Methods: Fibroblast-like synoviocytes (FLS) were collected from patients with RA and osteoarthritis (OA). miR-124-3p mimic was transfected into the RA FLS (RA miR-124 FLS). Exosomes were collected from the culture medium by ultracentrifugation. Macrophages were produced from THP-1 cells. MicroRNAs in the exosomes were analyzed using real-time PCR. Proteomics analysis was performed using nanoscale liquid chromatography-tandem mass spectrometry. Macrophage migration was evaluated using a Transwell migration assay. SiRNA was used to knockdown proteins of interest. Results: MicroRNAs in the RA FLS, RA miR-124 FLS, and OA FLS exosomes were similar. Proteomics analysis revealed that pentraxin 3 (PTX3) levels were higher in RA FLS exosomes than in RA miR-124 FLS and OA FLS exosomes, and proteasome 20S subunit beta 5 (PSMB5) levels were lower in RA FLS exosomes than in RA miR-124 FLS and OA FLS exosomes. The RA FLS exosomes promoted and the RA miR-124 FLS exosomes suppressed macrophage migration. PTX3-silenced RA FLS exosomes suppressed and PSMB5-silenced OA FLS exosomes promoted macrophage migration. Conclusions: RA FLS exosomes promote macrophage migration via PTX3 and PSMB5, and miR-124-3p suppresses this migration. |
| first_indexed | 2024-04-09T15:18:07Z |
| format | Article |
| id | doaj.art-4857de2d517c4485a6bd49daf339a326 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-09T15:18:07Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-4857de2d517c4485a6bd49daf339a3262023-04-29T14:52:48ZengElsevierHeliyon2405-84402023-04-0194e14986Exosomes derived from synovial fibroblasts from patients with rheumatoid arthritis promote macrophage migration that can be suppressed by miR-124-3pYuji Nakamachi0Kenichi Uto1Shinya Hayashi2Takaichi Okano3Akio Morinobu4Ryosuke Kuroda5Seiji Kawano6Jun Saegusa7Department of Clinical Laboratory, Kobe University Hospital, 7-5-2, Kusunoki cho, Chuo Ku, Kobe 650-0017, Japan; Corresponding author. Kobe University School of Medicine, Center for Advancement of Community Medicine, 2-1-5, Arata Cho, Hyogo ku, Kobe 652-0032, Japan.Department of Clinical Laboratory, Kobe University Hospital, 7-5-2, Kusunoki cho, Chuo Ku, Kobe 650-0017, JapanDepartment of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki cho, Chuo Ku, Kobe 650-0017, JapanDepartment of Clinical Laboratory, Kobe University Hospital, 7-5-2, Kusunoki cho, Chuo Ku, Kobe 650-0017, Japan; Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki cho, Chuo Ku, Kobe 650-0017, JapanDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki cho, Chuo Ku, Kobe 650-0017, JapanDepartment of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki cho, Chuo Ku, Kobe 650-0017, JapanDepartment of Medical Education, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki cho, Chuo Ku, Kobe 650-0017, JapanDepartment of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki cho, Chuo Ku, Kobe 650-0017, JapanObjectives: Exosomes are potent vehicles for intercellular communication. Rheumatoid arthritis (RA) is a chronic systemic disease of unknown etiology. Local administration of miR-124 precursor to rats with adjuvant-induced arthritis suppresses systemic arthritis and bone destruction. Thus, exosomes may be involved in this disease. We aimed to determine the role of exosomes in the pathology of RA. Methods: Fibroblast-like synoviocytes (FLS) were collected from patients with RA and osteoarthritis (OA). miR-124-3p mimic was transfected into the RA FLS (RA miR-124 FLS). Exosomes were collected from the culture medium by ultracentrifugation. Macrophages were produced from THP-1 cells. MicroRNAs in the exosomes were analyzed using real-time PCR. Proteomics analysis was performed using nanoscale liquid chromatography-tandem mass spectrometry. Macrophage migration was evaluated using a Transwell migration assay. SiRNA was used to knockdown proteins of interest. Results: MicroRNAs in the RA FLS, RA miR-124 FLS, and OA FLS exosomes were similar. Proteomics analysis revealed that pentraxin 3 (PTX3) levels were higher in RA FLS exosomes than in RA miR-124 FLS and OA FLS exosomes, and proteasome 20S subunit beta 5 (PSMB5) levels were lower in RA FLS exosomes than in RA miR-124 FLS and OA FLS exosomes. The RA FLS exosomes promoted and the RA miR-124 FLS exosomes suppressed macrophage migration. PTX3-silenced RA FLS exosomes suppressed and PSMB5-silenced OA FLS exosomes promoted macrophage migration. Conclusions: RA FLS exosomes promote macrophage migration via PTX3 and PSMB5, and miR-124-3p suppresses this migration.http://www.sciencedirect.com/science/article/pii/S240584402302193XRheumatoid arthritisFibroblast-like synoviocytesExosomemiR-124-3pMacrophageMigration |
| spellingShingle | Yuji Nakamachi Kenichi Uto Shinya Hayashi Takaichi Okano Akio Morinobu Ryosuke Kuroda Seiji Kawano Jun Saegusa Exosomes derived from synovial fibroblasts from patients with rheumatoid arthritis promote macrophage migration that can be suppressed by miR-124-3p Heliyon Rheumatoid arthritis Fibroblast-like synoviocytes Exosome miR-124-3p Macrophage Migration |
| title | Exosomes derived from synovial fibroblasts from patients with rheumatoid arthritis promote macrophage migration that can be suppressed by miR-124-3p |
| title_full | Exosomes derived from synovial fibroblasts from patients with rheumatoid arthritis promote macrophage migration that can be suppressed by miR-124-3p |
| title_fullStr | Exosomes derived from synovial fibroblasts from patients with rheumatoid arthritis promote macrophage migration that can be suppressed by miR-124-3p |
| title_full_unstemmed | Exosomes derived from synovial fibroblasts from patients with rheumatoid arthritis promote macrophage migration that can be suppressed by miR-124-3p |
| title_short | Exosomes derived from synovial fibroblasts from patients with rheumatoid arthritis promote macrophage migration that can be suppressed by miR-124-3p |
| title_sort | exosomes derived from synovial fibroblasts from patients with rheumatoid arthritis promote macrophage migration that can be suppressed by mir 124 3p |
| topic | Rheumatoid arthritis Fibroblast-like synoviocytes Exosome miR-124-3p Macrophage Migration |
| url | http://www.sciencedirect.com/science/article/pii/S240584402302193X |
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