We investigated the role of the inducible isoform of cyclooxyorenase (COX-2
) in a rat model of periodontitis using a selective COX-2 inhibitor NS-398.
Periodontitis was produced by a silk ligature placed around the lower left
I st molar. Animals were treated with NS-398 (3 mg kg(-1) i.p., 2 times pe
r day for 7 days) or vehicle. At Day 8, the gingivomucosal tissues encircli
ng the mandibular 1st molars were removed on both sides for COX-2 immunohis
tochemistry, measurement of plasma extravasation by the Evans blue techniqu
e, and alveolar bone loss by videomicroscopy. Immunohistochemical analysis
revealed numerous strongly COX-2-positive cells in the subepithelial tissue
s in the ligated side and only a few COX-2-reactive cells in the contralate
ral (control) side. Ligation significantly increased Evans blue extravasati
on in the gingivomucosal tissue and alveolar bone destruction compared to t
he control side. NS-398 treatment significantly reduced the plasma extravas
ation and alveolar bone resorption of the ligated side compared to vehicle
administration. The present results suggest that COX-2 is induced by period
ontitis, and plays an important role in gingival inflammation and alveolar
bone destruction. In a previous study (Br J Pharmacol 1998; 123:353-60) we
found the expression of the inducible isoform of nitric oxide synthase in t
his model. Therefore, based on our own data and the literature, we propose
that selective inhibition of these inducible enzymes might be a basis for a
djunctive therapy, or new therapeutic approaches in periodontitis. (C) 2001
Elsevier Science Inc. All rights reserved.