title: Low Shear Stress Attenuates COX-2 Expression Induced by Resistin in Human Osteoarthritic Chondrocytes.
abstract: Low shear stress has been proposed to play a reparative role in modulating cartilage homeostasis. Recently, epidemiological studies have found a positive correlation between the resistin level in serum and synovial fluid and osteoarthritis (OA) severity in patients. However, the effect of moderate shear stress on the catabolic stimulation of resistin in OA chondrocytes remains unclear. Hence, this study was to investigate whether low shear stress could regulate resistin-induced catabolic cyclooxygenase (COX)-2 expression in human OA chondrocytes and the underlying mechanism. Human OA chondrocytes and SW1353 chondrosarcoma cells were used in this study. Two modes of low shear stress (2 dyn/cm2), pre-shear and post-shear, were applied to the chondrocytes. A specific activator and siRNAs were used to investigate the mechanism of low shear stress-regulated COX-2 expression of resistin induction. We found that human OA chondrocytes exposed to different modes of low shear stress elicit an opposite effect on resistin-induced COX-2 expression: pre-shear for a short duration attenuates the resistin effect by inhibiting the transcription factor nuclear factor (NF)-κB-p65 subunit and the cAMP response element binding protein; however, post-shear over a longer duration enhances the resistin effect by activating only the NF-κB-p65 subunit. Moreover, our results demonstrated that the regulation of both shear modes in resistin-stimulated COX-2 expression occurs through increasing AMP-activated protein kinase activation and then sirtuin 1 expression. This study elucidates the detailed mechanism of low shear stress regulating the resistin-induced catabolic COX-2 expression and indicates a possible reparative role of moderate shear force in resistin-stimulated OA development. J. Cell. Physiol. 232: 1448-1457, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Orthopaedics and Traumatology, Veterans General Hospital, Taipei, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Su
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan.
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Chen
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan.
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Chang
authors.affiliation: Department of Orthopaedics, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan.
authors.forename: Kuo-Chin
authors.initials: KC
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan.
authors.forename: Chin-Chang
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedics and Traumatology, Veterans General Hospital, Taipei, Taiwan.|Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Fang-Yao
authors.initials: FY
authors.lastname: Chiu
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
authors.forename: Ko-Chao
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chun-Min
authors.initials: CM
authors.lastname: Lo
authors.affiliation: Department of Medical Research and Development, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan.
authors.forename: Shun-Fu
authors.initials: SF
authors.lastname: Chang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000368:Aged; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D010003:Osteoarthritis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D052243:Resistin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; C499624:RETN protein, human; D052243:Resistin; D051546:Cyclooxygenase 2; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1