Effect of hypoxia/reoxygenation on the cytokine-induced production of nitric oxide and superoxide anion in cultured osteoarthritic synoviocytes

被引:25
作者
Chenevier-Gobeaux, C. [1 ]
Simonneau, C. [1 ]
Lemarechal, H. [1 ]
Bonnefont-Rousselot, D. [2 ,3 ]
Poiraudeau, S. [4 ]
Rannou, F. [4 ,5 ]
Ekindjian, O. G. [1 ]
Anract, P. [6 ]
Borderie, D. [1 ,3 ]
机构
[1] Grp Hosp Cochin Broca Hotel Dieu, AP HP, Lab Biochim, F-75679 Paris 14, France
[2] Grp Hosp Pitie Salpetriere Charles Foix, AP HP, Serv Biochim Metab, F-75651 Paris 13, France
[3] Univ Paris 05, EA4466, Sorbonne Paris Cite, Fac Pharm, F-75270 Paris 06, France
[4] Grp Hosp Cochin Broca Hotel Dieu, AP HP, Serv Reeduc & Readaptat Fonct Appareil Locomoteur, F-75679 Paris 14, France
[5] Univ Paris 05, INSERM, UMR 747, Sorbonne Paris Cite, F-75006 Paris, France
[6] Grp Hosp Cochin Broca Hotel Dieu, AP HP, Serv Orthopedie, F-75679 Paris 14, France
关键词
Hypoxia/reoxygenation; Osteoarthritis; Nitric oxide; Inducible NO synthase; Synoviocytes; NADPH oxidase; ARTICULAR-CARTILAGE; BONE-SCINTIGRAPHY; EMISSION-TOMOGRAPHY; KNEE; MODEL; SPECT; DEGENERATION; PINHOLE; INJURY; RATS;
D O I
10.1016/j.joca.2013.03.010
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
100224 [整形外科学];
摘要
Objective: Hypoxia/reoxygenation (H/R) is an important feature in the osteoarthritis (OA) physiopathology. Nitric oxide ((NO)-N-center dot) is a significant proinflammatory mediator in the inflamed synovium. The purpose of this study was to investigate the effects of H/R on inducible NO synthase (iNOS) activity and expression in OA synoviocytes. In addition we studied the relationship between nitrosative stress and NADPH oxidase (NOX) in such conditions. Methods: Human cultured synoviocytes from OA patients were treated for 24 h with interleukin 1-beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) or neither; for the last 6 h, they were submitted to either normoxia or three periods of 1-h of hypoxia followed by 1-h of reoxygenation. (NO)-N-center dot metabolism (iNOS expression, nitrite and peroxynitrite measurements) was investigated. Furthermore, superoxide anion O-2(center dot-) production, NOX subunit expression and nitrosylation were also assessed. Results: iNOS expression and nitrite (but not peroxynitrite) production were significantly increased under H/R conditions when compared with to normoxia (P < 0.05). H/R conditions decreased O-2(center dot-) production from similar to 0.20 to similar to 0.12 nmol min(-1) mg proteins(-1) (P < 0.05), while NOXs' subunit expression and p47-phox phosphorylation were increased. NOXs and p47-phox were dramatically nitrosylated under H/R conditions (P < 0.05 vs normoxia). Using NOS inhibitors under H/R conditions, p47-phox nitrosylation was prevented and O-2(center dot-) production was restored at normoxic levels (0.21 nmol min(-1) mg of proteins(-1)). Conclusions: Our results provide evidence for an up-regulation of iNOS activity in OA synoviocytes under H/R conditions, associated to a down-regulation of NOX activity through nitrosylation. These findings highlight the importance of radical production to OA pathogenesis, and appraise the metabolic modifications of synovial cells under hypoxia. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:874 / 888
页数:15
相关论文
共 26 条
[1]
High-resolution imaging of progressive articular cartilage degeneration [J].
Adams, SB ;
Herz, PR ;
Stamper, DL ;
Roberts, MJ ;
Bourquin, S ;
Patel, NA ;
Schneider, K ;
Martin, SD ;
Shortkroff, S ;
Fujimoto, JG ;
Brezinski, ME .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2006, 24 (04) :708-715
[2]
The pinhole: gateway to ultra-high-resolution three-dimensional radionuclide imaging [J].
Beekman, Freek ;
van der Have, Frans .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2007, 34 (02) :151-161
[3]
Bone scintigraphy in chronic knee pain:: comparison with magnetic resonance imaging [J].
Boegård, T ;
Rudling, O ;
Dahlström, J ;
Dirksen, H ;
Petersson, IF ;
Jonsson, K .
ANNALS OF THE RHEUMATIC DISEASES, 1999, 58 (01) :20-26
[4]
Boegård T, 1998, ACTA RADIOL, V39, P7
[5]
Cartilage damage pattern in relation to subchondral plate thickness in a collagenase-induced model of osteoarthritis [J].
Botter, S. M. ;
van Osch, G. J. V. M. ;
Waarsing, J. H. ;
van der Linden, J. C. ;
Verhaar, J. A. N. ;
Pols, H. A. P. ;
van Leeuwen, J. P. T. M. ;
Weinans, H. .
OSTEOARTHRITIS AND CARTILAGE, 2008, 16 (04) :506-514
[6]
Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis [J].
Christiansen, B. A. ;
Anderson, M. J. ;
Lee, C. A. ;
Williams, J. C. ;
Yik, J. H. N. ;
Haudenschild, D. R. .
OSTEOARTHRITIS AND CARTILAGE, 2012, 20 (07) :773-782
[7]
Cook GJR, 1996, J NUCL MED, V37, P1353
[8]
Design and performance of a multi-pinhole collimation device for small animal imaging with clinical SPECT and SPECT-CT scanners [J].
DiFilippo, Frank P. .
PHYSICS IN MEDICINE AND BIOLOGY, 2008, 53 (15) :4185-4201
[9]
Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: An animal model of osteoarthritis [J].
Guzman, RE ;
Evans, MG ;
Bove, S ;
Morenko, B ;
Kilgore, K .
TOXICOLOGIC PATHOLOGY, 2003, 31 (06) :619-624
[10]
SPECT scan is a reliable tool for selection of patients undergoing unicompartmental knee arthroplasty [J].
Hart, Radek ;
Konvicka, Milan ;
Filan, Peter ;
deCordeiro, Jose .
ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY, 2008, 128 (07) :679-682