Effects and mechanisms of synovial mesenchymal stem cell–derived extracellular vesicular LncRNA-SNHG14 on chondrocyte injury

To investigate the effect of synovial mesenchymal stem cell (SMSC) derived extracellular vesicles (EVs) long non-coding ribonucleic acid (LncRNA) nuclear small RNA host gene 14 (SNHG14) on chondrocyte injury and its potential mechanism. EVs of SMSC were isolated and identified by transmission electron microscopy, nanoparticle tracking analysis, Western blot and EVs uptake test. Chondrocytes induced by interleukin-1β (IL-1β) were treated with EVs isolated from SMSCs transfected with sh-NC or sh-SNHG14. The proliferation and apoptosis of rat chondrocytes were detected by CCK-8 test and flow cytometry. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) were detected by ELISA. Western blot was used to detect the expression of apoptosis-related proteins [Bcl-2-related X protein (Bax), cysteine aspartate protease-3 (caspase-3), cytochrome C (Cyt c )], chondrocyte proliferation and regeneration-related proteins [sex-determining region Y-box protein 9 (SOX9), matrix metalloproteinase-13 (MMP-13), collagen type II alpha 1 (COL2A1), basic fibroblast growth factor (bFGF)]. The effect of LncRNA-SNHG14 on high mobility group protein B1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) signaling pathway was analyzed. By activating the pathway, its effect on the expression of LncRNA-SNHG14 and its effect on the above indicators were analyzed. LncRNA-SNHG14 in SMSC could be enriched and secreted in EVs, and chondrocytes can successfully uptake EVs. The expression level of LncRNA-SNHG14 in rat chondrocytes induced by IL-1β was increased, the cell survival rate was decreased, the apoptosis rate, TNF-α, IL-6 levels and Bax, caspase-3, Cytc, MMP-13 protein levels were increased, IGF-1 level and SOX9, COL2A1, bFGF protein levels were decreased, HMGB1, TLR4, NF-κB mRNA and protein levels were increased ( P < 0.05). SMSC-EVs silencing LncRNA-SNHG14 increased cell survival rate, decreased apoptosis rate and Bax, caspase-3, Cytc, MMP-13 protein levels, and decreased TNF-α, IL-6 levels and HMGB1, TLR4, NF-κB expression levels, increased IGF-1 level and SOX9, COL2A1, bFGF protein levels ( P < 0.05); after HMGB1 overexpression, the expression level of LncRNA-SNHG14 increased, the cell survival rate decreased, the apoptosis rate and the protein levels of Bax, caspase-3, Cytc and MMP-13 increased, the levels of IGF-1, SOX9, COL2A1 and bFGF decreased, and the levels of TNF-α and IL-6 increased ( P < 0.05). SMSC-EVs silencing LncRNA-SNHG14 can promote chondrocyte proliferation, inhibit chondrocyte apoptosis and inflammatory response in an in vitro model of IL-1β-induced chondrocyte injury. These effects are associated with reduced expression of HMGB1/TLR4/NF-κB pathway components, suggesting the involvement of this pathway.