title: Chondroprotective role of sesamol by inhibiting MMPs expression via retaining NF-κB signaling in activated SW1353 cells.
abstract: Overexpression of matrix metalloproteinases (MMPs) is a major pathological factor causing cartilage destruction in osteoarthritis (OA). This study aimed to investigate the effects and mechanisms of sesamol on expression of MMPs in activated chondrosarcoma cells. Sesamol significantly attenuated TNF-α- and IL-1β-induced gelatinolysis and expression of MMP-9 in a concentration-dependent manner in SW1353 cells. Additionally, both MMP-1 and -13 stimulated by PMA were inhibited by sesamol. On the other hand, the NF-κB signaling activation through IκB-α degradation was restored by sesamol under TNF-α or PMA stimulation. Furthermore, this bioactive compound exerted the reduction on phosphorylation of ERK1/2 or p38 MAPKs after either PMA or IL-1β stimulation. This study also evaluated whether sesamol down-regulates MMP expression in the joint cartilage of monosodium iodoacetate (MIA)-induced OA in rats. Sesamol prevented the expression of MMP-1 and -9 in the cartilage of MIA-induced OA in rats. The results of this study demonstrate that sesamol inhibits cytokine- or PMA-induced MMPs expression through the signal pathways of either NF-κB or ERK/p38 MAPKs down-regulation. This study also showed that sesamol attenuates destructive factor expression in vivo, providing a potential strategy for the chondroprotective therapy in OA.
authors.affiliation: Department of Orthopaedic Surgery, Mackay Memorial Hospital, Department of Leisure Sports and Health Management, College of Humanities and Sciences, St. John's University, Taipei, Taiwan.
authors.forename: Yung-Chang
authors.initials: YC
authors.lastname: Lu
authors.forename: Thanasekaran
authors.initials: T
authors.lastname: Jayakumar
authors.forename: Yeh-Fang
authors.initials: YF
authors.lastname: Duann
authors.forename: Yung-Chen
authors.initials: YC
authors.lastname: Chou
authors.forename: Cheng-Ying
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Shin-Yun
authors.initials: SY
authors.lastname: Yu
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
authors.forename: George
authors.initials: G
authors.lastname: Hsiao
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D052117:Benzodioxoles; D016328:NF-kappa B; D010636:Phenols; D020011:Protective Agents; C025583:sesamol; D020782:Matrix Metalloproteinases