![]() ![]() Large scaled studies have revealed strong correlations between the deposition of MSU crystals and cartilage lesions. Cartilage injury is a serious complication of gout arthritis and MSU crystals have profound inhibitory effects on chondrocyte viability and function. Subjects with high MSU levels have focal erosions, osteophytes, and bone marrow lesions. Gout arthritis, the most common inflammatory arthropathy in young men, is characterized by the deposition of monosodium urate (MSU) crystals in joints. These results indicate that downregulation of Sox8 plays an important role in MSU-induced chondrocyte autophagy by modulating PI3K/AKT/mTOR signaling, and overexpression of Sox8 may serve as a novel therapy to prevent the impairment of cartilage in gout arthritis. In vivo, overexpression of Sox8 remarkably alleviated cartilage damage in acute gouty model rats. Overexpression of Sox8 notably inhibited MSU crystal-induced autophagy by rescuing the phosphorylation levels in the PI3K/AKT/mTOR signaling pathway. In chondrocytes, MSU crystals reduced the expression of Sox8, inhibited the PI3K/AKT/mTOR signaling pathway, and increased the level of autophagy. The expression of Sox8 was significantly downregulated both in vivo and in vitro. In vivo, the effect of Sox8 on cartilage of acute gouty model rats was evaluated by safranin-O/fast green staining and Western blot. ![]() The ratio of LC3-II/I in the presence or absence of bafilomycin A1 and the expression levels of Beclin1, Sox8, p-PI3K, PI3K, p-AKT, AKT, p-mTOR, and mTOR were detected by Western blot. ![]() The morphology of autophagosomes was observed by transmission electron microscopy. The autophagic vacuoles were stained with monodansylcadaverine and examined by flow cytometry. Transfection of the mRFP-GFP-LC3 plasmid was evaluated by confocal microscopy. The recombinant Sox8 lentiviral vector (lenti-Sox8) was applied to upregulate the expression of Sox8. MSU crystal-treated human chondrocytes were used to evaluate the function of Sox8. mRNAs of cartilage from MSU-induced gouty arthritis rat model were sequenced. This study aimed to investigate whether MSU crystal-induced cartilage impairment was related to autophagic signaling. The deposition of monosodium urate (MSU) crystals in arthritic joints of gout seriously damages cartilage. ![]()
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