Document Detail


The effects of selective COX-2 inhibitor/celecoxib and omega-3 fatty acid on matrix metalloproteinases, TIMP-1, and laminin-5gamma2-chain immunolocalization in experimental periodontitis.
MedLine Citation:
PMID:  18834249     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Matrix metalloproteinases (MMPs) play important roles in tissue-destruction mechanisms-associated periodontitis. MMP-8 and -13 are the predominant collagenases that are important in the extracellular matrix degradation in periodontal tissues. MMP-14 is a membrane-type MMP, whereas laminin-5 indicates basal membrane modification and epithelial induction. The purpose of the present study was to evaluate the effects of celecoxib and omega-3 fatty acid administration on the gingival tissue expression of MMP-8, -13, and -14, tissue inhibitor of MMP (TIMP)-1, and laminin (Ln)-5gamma2-chain in rat experimental periodontitis induced by Escherichia coli endotoxin (lipopolysaccharide [LPS]). METHODS: Experimental periodontitis was induced in rats by repeated LPS injection. Fifty-one adult male Sprague-Dawley rats were divided into six study groups: saline control, LPS, LPS + celecoxib, LPS + therapeutic omega-3 (TO3), prophylactic omega-3 + LPS + omega-3 (P+TO3), and LPS + celecoxib + omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given as a single agent or as combination therapy for 14 days. On day 15, all rats were sacrificed, and gingival tissues were analyzed immunohistochemically for the expression of MMP-8, -13, and -14, TIMP-1, and Ln-5gamma2-chain. Alveolar bone loss was evaluated morphometrically under a stereomicroscope. Data were tested statistically by Kruskal-Wallis and Mann-Whitney tests and Spearman correlation analysis. RESULTS: Alveolar bone loss was significantly higher in all study groups compared to the saline control group (all P <0.01). MMP-8 expression was significantly higher in the LPS group than in the saline group (P = 0.001). Very low expression of MMP-8 was found in the celecoxib, P+TO3, and combination groups. TO3 increased TIMP-1 expression significantly compared to the LPS group (P <0.05). Individual celecoxib and P+TO3 administration increased MMP-14 significantly compared to saline control and LPS groups (P <0.05). No significant differences were found among the study groups with regard to Ln-5gamma2-chain and MMP-13 expressions (P >0.05). CONCLUSIONS: Selective cyclooxygenase-2 inhibitor, prophylactic omega-3 fatty acid, and a combination of these two agents can inhibit gingival tissue MMP-8 expression. Moreover, the individual administration of therapeutic omega-3 may increase gingival TIMP-1 expression in contrast to no effect on MMP-8, -13, and -14 expressions in experimental periodontitis. These experimental findings in a rat model of LPS-induced periodontitis need to be verified by clinical human studies.
Authors:
Saynur Vardar-Sengul; Eralp Buduneli; Oya Turkoglu; Nurcan Buduneli; Gül Atilla; Jaana Wahlgren; Timo Sorsa; Haluk Baylas
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of periodontology     Volume:  79     ISSN:  0022-3492     ISO Abbreviation:  J. Periodontol.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-06     Completed Date:  2009-01-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8000345     Medline TA:  J Periodontol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1934-41     Citation Subset:  D; IM    
Affiliation:
Department of Periodontology, School of Dentistry, Ege University, Izmir, Turkey. saynurvardar@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Alveolar Bone Loss / drug therapy,  enzymology,  pathology
Animals
Cyclooxygenase 2 Inhibitors / therapeutic use*
Disease Models, Animal
Drug Combinations
Escherichia coli
Fatty Acids, Omega-3 / therapeutic use*
Gingiva / drug effects,  enzymology
Gingivitis / drug therapy,  enzymology,  pathology
Laminin / analysis,  drug effects*
Lipopolysaccharides
Male
Matrix Metalloproteinase 13 / analysis,  drug effects
Matrix Metalloproteinase 14 / analysis,  drug effects
Matrix Metalloproteinase 8 / analysis,  drug effects
Matrix Metalloproteinases / analysis,  drug effects*
Periodontitis / drug therapy*,  enzymology,  pathology
Pyrazoles / therapeutic use*
Rats
Rats, Sprague-Dawley
Sulfonamides / therapeutic use*
Tissue Inhibitor of Metalloproteinase-1 / analysis,  drug effects*
Chemical
Reg. No./Substance:
0/Cyclooxygenase 2 Inhibitors; 0/Drug Combinations; 0/Fatty Acids, Omega-3; 0/Laminin; 0/Lipopolysaccharides; 0/Pyrazoles; 0/Sulfonamides; 0/Tissue Inhibitor of Metalloproteinase-1; 169590-42-5/celecoxib; EC 3.4.24.-/Matrix Metalloproteinase 13; EC 3.4.24.-/Matrix Metalloproteinases; EC 3.4.24.-/Mmp13 protein, rat; EC 3.4.24.34/Matrix Metalloproteinase 8; EC 3.4.24.80/Matrix Metalloproteinase 14

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


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