Document Detail


The chondroprotective effect of selective COX-2 inhibition in osteoarthritis: ex vivo evaluation of human cartilage tissue after in vivo treatment.
MedLine Citation:
PMID:  18926729     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Recent in vitro studies showed that celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, protects human osteoarthritic cartilage tissue from degeneration. The objective was to substantiate these beneficial effects in an in vivo (clinical) study with celecoxib treatment of patients with severe knee osteoarthritis (OA) and subsequent evaluation of cartilage tissue ex vivo. METHODS: Patients with knee OA were treated 4 weeks prior to total knee replacement surgery with either celecoxib 200mg b.d., indomethacin 50mg b.d., or received no treatment. During surgery cartilage and synovium were collected and analyzed in detail ex vivo. RESULTS: When compared to non-treated patients, patients treated with celecoxib showed significant beneficial effects on proteoglycan synthesis, -release, and -content, confirming the in vitro data. In the indomethacin group, no significant differences were found compared to the control group. On the contrary, a tendency towards a lower content and lower synthesis rate was found. In the treated groups prostaglandin-E(2) levels were lower than in the control group, indicating COX-2 inhibition. Ex vivo release of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha by synovial tissue was decreased by treatment with celecoxib, whereas in the indomethacin group only IL-1 beta release was decreased. CONCLUSION: Using this novel approach we were able to demonstrate an in vivo generated chondrobeneficial effect of celecoxib in patients with end stage knee OA.
Authors:
T N de Boer; A M Huisman; A A Polak; A G Niehoff; A C van Rinsum; D Saris; J W J Bijlsma; F J P G Lafeber; S C Mastbergen
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2008-10-15
Journal Detail:
Title:  Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society     Volume:  17     ISSN:  1522-9653     ISO Abbreviation:  Osteoarthr. Cartil.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-13     Completed Date:  2010-01-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9305697     Medline TA:  Osteoarthritis Cartilage     Country:  England    
Other Details:
Languages:  eng     Pagination:  482-8     Citation Subset:  IM    
Affiliation:
Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. t.n.deboer-4@umcutrecht.nl
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MeSH Terms
Descriptor/Qualifier:
Aged
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
Arthroplasty, Replacement, Knee
Cartilage, Articular / drug effects*,  metabolism,  pathology
Cyclooxygenase 2 Inhibitors / therapeutic use*
Dinoprostone / biosynthesis
Female
Humans
Indomethacin / therapeutic use
Interleukin-1beta / metabolism
Male
Matrix Metalloproteinases / metabolism
Middle Aged
Nitric Oxide / biosynthesis
Osteoarthritis, Knee / drug therapy*,  metabolism,  pathology,  surgery
Proteoglycans / metabolism
Pyrazoles / therapeutic use
Sulfonamides / therapeutic use
Synovial Membrane / drug effects,  metabolism
Tumor Necrosis Factor-alpha / metabolism
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Cyclooxygenase 2 Inhibitors; 0/Interleukin-1beta; 0/Proteoglycans; 0/Pyrazoles; 0/Sulfonamides; 0/Tumor Necrosis Factor-alpha; 10102-43-9/Nitric Oxide; 169590-42-5/celecoxib; 363-24-6/Dinoprostone; 53-86-1/Indomethacin; EC 3.4.24.-/Matrix Metalloproteinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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