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Bone Marrow Mesenchymal Stem Cells Release miR-378a-5p-Carried Extracellular Vesicles to Alleviate Rheumatoid Arthritis.


ABSTRACT: This study investigates whether bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) can affect rheumatoid arthritis (RA) by delivering microRNA (miR)-378a-5p to regulate the IRF1/STAT1 axis. We identified RA-associated miRNAs using GEO microarray dataset GSE121894. We found the most important miRNAs in RA synovial tissues using RT-qPCR. BMSCs-derived EVs were ultracentrifuged and co-cultured with HSMECs in vitro. Dual-luciferase and RIP studies examined miR-378a-5p's specific binding to IRF1. We also measured angiogenesis, migration, and proliferation using CCK-8, Transwell, and tube formation assays. CIA (collagen-induced arthritis) mice models were created by inducing arthritis and scoring it. RA synovial tissues had low miR-378a-5p expression, whereas BMSC-derived EVs had high levels. The transfer of miR-378a-5p by BMSC-derived EVs to HSMECs boosted proliferation, migration, and angiogenesis. miR-378a-5p inhibited IRF1. MiR-378a-5p-containing BMSC-derived EVs decreased STAT1 phosphorylation and HSMEC IRF1 expression. EVs with miR-378a-5p mimic promoted HSMEC proliferation, migration, and angiogenesis, whereas dexmedetomidine inhibited STAT1 phosphorylation. In CIA mice, BMSC-derived EVs containing miR-378a-5p enhanced synovial vascular remodeling and histopathology. Thus, miR-378a-5p from BMSC-derived EVs promotes HSMEC proliferation, migration, and angiogenesis, inactivating the IRF1/STAT1 axis and preventing rheumatoid arthritis.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC10715757 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Bone Marrow Mesenchymal Stem Cells Release miR-378a-5p-Carried Extracellular Vesicles to Alleviate Rheumatoid Arthritis.

Zhang Yaqin Y   Jiao Ziying Z   Wang Shanshan S  

Journal of innate immunity 20231103 1


This study investigates whether bone marrow mesenchymal stem cell (BMSC)-derived extracellular vesicles (EVs) can affect rheumatoid arthritis (RA) by delivering microRNA (miR)-378a-5p to regulate the interferon regulatory factor 1/signal transducer and transcription 1 (IRF1/STAT1) axis. We identified RA-associated miRNAs using the GEO microarray dataset GSE121894. We found the most important miRNAs in RA synovial tissues using RT-qPCR. BMSC-derived EVs were ultracentrifuged and cocultured with h  ...[more]

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