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Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-?B pathway.

ABSTRACT: Osteoarthritis is a disease with inflammatory and catabolic imbalance in cartilage. Dihydroartemisinin (DHA), a natural and safe anti-malarial agent, has been reported to inhibit inflammation, but its effects on chondrocytes have yet to be elucidated. We investigated the effects of DHA on catabolism in chondrocytes. Viability of SD rats chondrocytes was analyzed. Autophagy levels were determined via expression of autophagic markers LC3 and ATG5, GFP-LC3 analysis, acridine orange staining, and electron microscopy. ATG5 siRNA induced autophagic inhibition. Catabolic gene and chemokine expression was evaluated using qPCR. The NF-?B inhibitor SM7368 and p65 over-expression were used to analyze the role of NF-?B pathway in autophagic activation. A concentration of 1??M DHA without cytotoxicity increased LC3-II and ATG5 levels as well as autophagosomal numbers in chondrocytes. DHA inhibited TNF-?-induced expression of MMP-3 and -9, ADAMTS5, CCL-2 and -5, and CXCL1, which was reversed by autophagic inhibition. TNF-?-stimulated nuclear translocation and degradation of the p65 and I?B? proteins, respectively, were attenuated in DHA-treated chondrocytes. NF-?B inhibition activated autophagy in TNF-?-treated chondrocytes, but p65 over-expression reduced the autophagic response to DHA. These results indicate that DHA might suppress the levels of catabolic and inflammatory factors in chondrocytes by promoting autophagy via NF-?B pathway inhibition.

SUBMITTER: Jiang LB

PROVIDER: S-EPMC5150254 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB pathway.

Jiang Li-Bo LB Meng De-Hua DH Lee Soo-Min SM Liu Shu-Hao SH Xu Qin-Tong QT Wang Yang Y Zhang Jian J

Scientific reports 20161212

Osteoarthritis is a disease with inflammatory and catabolic imbalance in cartilage. Dihydroartemisinin (DHA), a natural and safe anti-malarial agent, has been reported to inhibit inflammation, but its effects on chondrocytes have yet to be elucidated. We investigated the effects of DHA on catabolism in chondrocytes. Viability of SD rats chondrocytes was analyzed. Autophagy levels were determined via expression of autophagic markers LC3 and ATG5, GFP-LC3 analysis, acridine orange staining, and el ...[more]

PMID: 27941926

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Dataset Information

Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-?B pathway.

Publications

Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB pathway.

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