The effects of nonsteroidal anti-inflammatory drugs on clinical outcomes, synovial fluid cytokine concentration and signal transduction pathways in knee osteoarthritis. A randomized open label trial

被引：114

作者：

Gallelli, L. ^{[1
]}

Galasso, O. ^{[2
]}

Falcone, D. ^{[1
]}

Southworth, S. ^{[3
]}

Greco, M. ^{[1
]}

Ventura, V. ^{[1
]}

Romualdi, P. ^{[4
]}

Corigliano, A. ^{[2
]}

Terracciano, R. ^{[1
]}

Savino, R. ^{[1
]}

Gulletta, E. ^{[1
]}

Gasparini, G. ^{[2
]}

De Sarro, G. ^{[1
]}

机构：

[1] Magna Graecia Univ Catanzaro, Sch Med, Dept Hlth Sci, I-88100 Catanzaro, Italy

[2] Magna Graecia Univ Catanzaro, Sch Med, Dept Orthoped & Trauma Surg, I-88100 Catanzaro, Italy

[3] PLLC, North Mississippi Sports Med & Orthoped Clin, Tupelo, MS USA

[4] Univ Bologna, Dept Pharmacol & Biotechnol, Bologna, Italy

来源：

OSTEOARTHRITIS AND CARTILAGE | 2013年 / 21卷 / 09期

关键词：

Knee osteoarthritis; NSAID; WOMAC score; Synovial fluid cytokines; Signal transduction pathways; FACTOR-KAPPA-B; PROSTAGLANDIN E-2; TNF-ALPHA; INTERLEUKIN-6; CELECOXIB; CARTILAGE; INFLAMMATION; CHONDROCYTES; SENSITIVITY; ACTIVATION;

D O I：

10.1016/j.joca.2013.06.026

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：

摘要：

Objective: We investigated the effects of celecoxib, diclofenac, and ibuprofen on the disease-specific quality of life, synovial fluid cytokines and signal transduction pathways in symptomatic knee osteoarthritis (OA). Design: Ninety patients scheduled for a total knee arthroplasty (TKA) were randomized to six groups that were treated with low and high dosages of celecoxib, diclofenac or ibuprofen. At the time of the first admission (T0) and at surgery (T1 = 14 days after beginning of the nonsteroidal anti-inflammatory drugs (NSAIDs)), samples of knee synovial fluid were obtained from each patient for analysis. During the surgery the synovial tissue was harvested from the knee of patients. The Western Ontario and McMaster universities (WOMAC) score was used to evaluate the patient disease-specific quality of life at T0 and T1. Microarray tests performed at T0 and T1 were used to evaluate the effects of NSAIDs on Tumor necrosis factor (TNE)-alpha, Interleukin-6 (IL-6), IL8 and Vascular endothelial growth factor (VEGF) concentration in the synovial fluid. Western blot assays evaluated the effects of NSAIDs on MAP kinase (MAPK) signal transduction pathway in the synovial membrane. Results: NSAID treatment induced a statistically significant improvement in the WOMAC score and a statistically significant decrease in the IL-6, VEGF and TNF-alpha concentration in the synovial fluid. Higher dosages of NSAIDs provided a greater improvement in the disease-specific quality of life of patients and lower concentrations of pro-inflammatory cytokines in the synovial fluid. Inhibition of MAPKs was noted after NSAID treatment. Conclusion: Short-term NSAID treatment improves the patient disease-specific quality of life with a parallel decrease in pro-inflammatory synovial fluid cytokine levels in knee OA. Signal transduction pathways may be involved in regulating the anti-inflammatory effects of NSAIDs. ClinicalTrial.gov: NCT01860833. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

引用

页码：1400 / 1408

页数：9

共 54 条

[31] A METHOD FOR ESTIMATING THE PROBABILITY OF ADVERSE DRUG-REACTIONS [J].

NARANJO, CA ;

BUSTO, U ;

SELLERS, EM ;

SANDOR, P ;

RUIZ, I ;

ROBERTS, EA ;

JANECEK, E ;

DOMECQ, C ;

GREENBLATT, DJ .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 1981, 30 (02) :239-245

[32] TNF-α and TNF-α receptor type 1 upregulation in glia and neurons after peripheral nerve injury -: Studies in murine DRG and spinal cord [J].

Ohtori, S ;

Takahashi, K ;

Moriya, H ;

Myers, RR .

SPINE, 2004, 29 (10) :1082-1088

[33]

Oliva F, 2010, FUNCT NEUROL, V23, P1

[34] Associations between proinflammatory cytokines in the synovial fluid and radiographic grading and pain-related scores in 47 consecutive patients with osteoarthritis of the knee [J].

Orita, Sumihisa ;

Koshi, Takana ;

Mitsuka, Takeshi ;

Miyagi, Masayuki ;

Inoue, Gen ;

Arai, Gen ;

Ishikawa, Tetsuhiro ;

Hanaoka, Eiji ;

Yamashita, Keishi ;

Yamashita, Masaomi ;

Eguchi, Yawara ;

Toyone, Tomoaki ;

Takahashi, Kazuhisa ;

Ohtori, Seiji .

BMC MUSCULOSKELETAL DISORDERS, 2011, 12

[35] DElevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis [J].

Pearle, A. D. ;

Scanzello, C. R. ;

George, S. ;

Mandl, L. A. ;

DiCarlo, E. F. ;

Peterson, M. ;

Sculco, T. P. ;

Crow, M. K. .

OSTEOARTHRITIS AND CARTILAGE, 2007, 15 (05) :516-523

[36]

Pelletier JP, 2004, OSTEOARTHRITIS CAR S, V12S, P63

[37] Effects of meloxicam, compared with other NSAIDs, on cartilage proteoglycan metabolism, synovial prostaglandin E-2, and production of interleukins 1, 6 and 8, in human and porcine explants in organ culture [J].

Rainsford, KD ;

Ying, C ;

Smith, FC .

JOURNAL OF PHARMACY AND PHARMACOLOGY, 1997, 49 (10) :991-998

[38] Is there an association between the use of different types of nonsteroidal antiinflammatory drugs and radiologic progression of osteoarthritis? The Rotterdam study [J].

Reijman, M ;

Bierma-Zeinstra, SMA ;

Pols, HAP ;

Koes, BW ;

Stricker, BHC ;

Hazes, JMW .

ARTHRITIS AND RHEUMATISM, 2005, 52 (10) :3137-3142

[39] IL1B gene promoter haplotype pairs predict clinical levels of interleukin-1β and C-reactive protein [J].

Rogus, John ;

Beck, James D. ;

Offenbacher, Steven ;

Huttner, Kenneth ;

Iacoviello, Licia ;

Latella, Maria Carmela ;

de Gaetano, Monica ;

Wang, Hwa-Ying ;

Kornman, Kenneth S. ;

Duff, Gordon W. .

HUMAN GENETICS, 2008, 123 (04) :387-398

[40] Pralnacasan, an inhibitor of interleukin-1β converting enzyme, reduces joint damage in two murine models of osteoarthritis [J].

Rudolphi, K ;

Gerwin, N ;

Verzijl, N ;

van der Kraan, P ;

van den Berg, W .

OSTEOARTHRITIS AND CARTILAGE, 2003, 11 (10) :738-746

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