Exosomes from mesenchymal stem cells (MSCs) show anti-inflammatory effect on osteoarthritis (OA); however, their biological effect and mechanism are not yet clearly understood. This study investigated the anti-inflammatory effect and mechanism of MSC-derived exosomes (MSC-Exo) primed with IL-1β in osteoarthritic SW982 cells.
SW982 cells were treated with interleukin (IL)-1β and tumor necrosis factor (TNF)-α to induce the OA phenotype. The effect of exosomes without priming (MSC-Exo) or with IL-1β priming (MSC-IL-Exo) was examined on the expression of pro- or anti-inflammatory factors, and the amount of IκBα was examined in SW982 cells. Exosomes were treated with RNase to remove RNA. The role of miR-147b was examined using a mimic and an inhibitor.
MSC-IL-Exo showed stronger inhibitory effects on the expression of pro-inflammatory cytokines (IL-1β, IL-6, and monocyte chemoattractant protein-1) than MSC-Exo. The expression of anti-inflammatory factors (SOCS3 and SOCS6) was enhanced by MSCs-IL-Exo. Priming with IL-1β increased RNA content in MSC-IL-Exo, and pretreatment with RNase abolished anti-inflammatory effect in SW982 cells. miR-147b was found in much larger amounts in MSC-IL-Exo than in MSC-Exo. The miR-147b mimic significantly inhibited the expression of inflammatory cytokines, while the miR-147b inhibitor only partially blocked the anti-inflammatory effect of MSC-IL-Exo. MSC-IL-Exo and miR-147b mimic inhibited the reduction of IκBα, an nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, by IL-1β and TNF-α.
This study showed that MSC exosomes with IL-1β priming exhibit significantly enhanced anti-inflammatory activity in osteoarthritic SW982 cells. The effect of IL-1β-primed MSC exosomes is mediated by miRNAs such as miR-147b and involves inhibition of the NF-κB pathway.
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This study was supported by the National Research Foundation Grant (NRF-2019M3E5D1A02070861) of the Korea government.
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Anti-inflammatory effect of MSC-derived exosomes primed with various factors. Exosomes isolated from MSCs were unprimed or primed with IL-1β, Poly I:C, IFN-γ, or TNF-α all at 10 μg/mL for 24 h. SW982 cells were treated with IL-1β (10 ng/mL) and TNF-α (25 ng/mL) for 24 h in the presence of each of the MSC-derived exosomes as indicated. mRNA levels of selected pro-inflammatory cytokines (IL-1b, IL-6, and MCP-1) were examined via RT-qPCR analysis. Values are normalized by that of GAPDH and presented as mean ± SD from three independent experiments (n = 3). #/*p < 0.05, ##/**p < 0.01, and ###/***p < 0.001 by one-way ANOVA for five treatment groups (Unprimed-Exo, IL-1β-Exo, poly I:C-Exo, IFN-γ-Exo, and TNF-α-Exo) versus untreated control (#) or versus IL-1β and TNF-α groups (*)
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Kim, M., Shin, D.I., Choi, B.H. et al. Exosomes from IL-1β-Primed Mesenchymal Stem Cells Inhibited IL-1β- and TNF-α-Mediated Inflammatory Responses in Osteoarthritic SW982 Cells. Tissue Eng Regen Med (2021). https://doi.org/10.1007/s13770-020-00324-x