title: Dihydroartemisinin inhibits catabolism in rat chondrocytes by activating autophagy via inhibition of the NF-κB 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-κB inhibitor SM7368 and p65 over-expression were used to analyze the role of NF-κB pathway in autophagic activation. A concentration of 1 μM DHA without cytotoxicity increased LC3-II and ATG5 levels as well as autophagosomal numbers in chondrocytes. DHA inhibited TNF-α-induced expression of MMP-3 and -9, ADAMTS5, CCL-2 and -5, and CXCL1, which was reversed by autophagic inhibition. TNF-α-stimulated nuclear translocation and degradation of the p65 and IκBα proteins, respectively, were attenuated in DHA-treated chondrocytes. NF-κB inhibition activated autophagy in TNF-α-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-κB pathway inhibition.
authors.affiliation: Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Jiang
authors.affiliation: Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: De-Hua
authors.initials: DH
authors.lastname: Meng
authors.affiliation: Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Soo-Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Shu-Hao
authors.initials: SH
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Qin-Tong
authors.initials: QT
authors.lastname: Xu
authors.affiliation: Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000008:administration & dosage*; D001343:Autophagy / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008660:Metabolism / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D037621:Artemisinins; D018836:Inflammation Mediators; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C039060:artenimol