Journal of cellular and molecular medicine
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The abundance of inflammatory mediators in injured joint indicates innate immune reactions activated during temporomandibular joint osteoarthritis (TMJOA) progression. Toll-like receptor 4 (TLR4) can mediate innate immune reaction. Herein, we aimed to investigate the expression profile and effect of TLR4 in the cartilage and subchondral bone of the discectomy-induced TMJOA mice. ⋯ Furthermore, TLR4 promotes the expression of MyD88/NFκB, pro-inflammatory and catabolic mediators in cartilage of discectomy-induced TMJOA. Besides, TLR4 participates in the production of MyD88/NFκB, pro-inflammatory and catabolic mediators in IL-1β-induced chondrocytes. TLR4 contributes to the damage of cartilage and subchondral bone in discectomy-induced TMJOA mice through activation of MyD88/NFκB and release of pro-inflammatory and catabolic mediators.
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Recent studies have shown that mesenchymal stem cell-derived exosome could attenuate ischaemia-reperfusion (I/R) injury by suppressing inflammatory response in the liver. Glycyrrhetinic acid was also shown to be capable of repressing the TLR4 signalling pathway. However, it remains to be explored as whether the combined administration of mesenchyma stem cell (MSC)-derived exosome and glycyrrhetinic acid (GA) could increase their therapeutic effects on I/R injury. ⋯ Combined treatment with MSC-derived exosome and GA effectively maintained the expression of key proteins involved in inflammatory response in LPS stimulated THP-1 cells and THP-1 cells treated under hypoxia conditions. In the established of I/R rat models, GA administration reinforced the therapeutic efficiency of MSC-derived exosomes by maintaining the proportion of different subgroups of peripheral blood cells, decreasing the concentration of ALT and AST, and restoring the expression of dysregulated proteins associated with inflammation. Our results demonstrated that treatment with exosomes derived from mesenchymal stem cells (MSCs) attenuated liver I/R injury, while the pre-treatment with GA may further promote the therapeutic effect of mesenchymal stem cell-derived exosome against acute liver ischaemia-reperfusion injury.