Effects and mechanisms of inflammatory exosomes on knee joint function and synovial tissue in normal white rabbits
Objective It is to observe the effect and mechanism of inflammatory exosomes on knee joint function and synovial tissue in normal white rabbits.Methods Ten male New Zealand large white rabbits were taken to establish the models of single knee osteoarthritis by modified Hluth method,and the exosomes were extracted from the modeled rabbit joint flushing fluid.Another 27 male New Zealand large white rabbits were taken and randomly divided into blank group,saline group and exosome group,with 9 rabbits in each group.The exosome group was injected with the extracted exosome suspension in the right knee joint cavity,and the saline group was injected with saline,both 3 times per week,continuously treated for 2 weeks and then observed for 4 weeks;the blank group was not treated.The behaviors and joint swelling of the white rabbits in each group were recorded,and the Lequesne index of knee osteoarthritis severity was calculated;the patho-logical morphology of synovial tissue was observed by HE staining,and the Krenn score of synovial tissue was calculated;the contents of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in the joint flushing fluid were detected by ELISA,and the protein expressions of related components of Toll-like receptors(TLRs)/nuclear factor-κB(NF-κB)path-way in synovial tissues were detected by Western blot.Results After the intervention,the white rabbits in the exosome group showed mild lameness,with mild swelling around the joint cavity,and their Lequesne index were significantly higher than those before the intervention and in the blank group and saline group(all P<0.05).HE staining of synovium showed that there were obvious proliferation of synovial tissue and blood vessels in white rabbits of the exosome group,with a large number of inflammatory cells infiltrating,and their Krenn scores were significantly higher than those in the blank group and the saline group(all P<0.05).The contents of TNF-α and IL-1β in the joint flushing fluid and the relative expressions of TLR2,TLR4,NF-κB p65 and MyD88 proteins in the synovial tissue of the exosome group were significantly higher than those of the blank group and saline group(all P<0.05).Conclusion Inflammatory exosomes can activate the TLRs/NF-κB signaling pathway in normal synovium tissue,induce the release of downstream inflammatory factors and leading to syno-vial inflammation formation.
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