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.
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.
Vardar-Sengul
Saynur
S
Department of Periodontology, School of Dentistry, Ege University, Izmir, Turkey. saynurvardar@yahoo.com
Buduneli
Eralp
E
Turkoglu
Oya
O
Buduneli
Nurcan
N
Atilla
Gül
G
Wahlgren
Jaana
J
Sorsa
Timo
T
Baylas
Haluk
H
D016301:Alveolar Bone Loss / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D000818:Animals; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004926:Escherichia coli; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005881:Gingiva / Q000187:drug effects / Q000201:enzymology; D005891:Gingivitis / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D007797:Laminin / Q000032:analysis / Q000187:drug effects*; D008070:Lipopolysaccharides; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000032:analysis / Q000187:drug effects; D053511:Matrix Metalloproteinase 14 / Q000032:analysis / Q000187:drug effects; D020784:Matrix Metalloproteinase 8 / Q000032:analysis / Q000187:drug effects; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000187:drug effects*; D010518:Periodontitis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000187:drug effects*
D052246:Cyclooxygenase 2 Inhibitors; D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D007797:Laminin; D008070:Lipopolysaccharides; D011720:Pyrazoles; D013449:Sulfonamides; D019715:Tissue Inhibitor of Metalloproteinase-1; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C507083:Mmp13 protein, rat; D020784:Matrix Metalloproteinase 8; D053511:Matrix Metalloproteinase 14; D000068579:Celecoxib