Discussion - References.
In this study, histologic evidence is presented which supports the finding that COX-2 expression is upregulated in radicular cysts. Strong immunostain for COX-2 was detected in endothelial cells, epithelial cells and cells with fibroblastmorphology. This observation is in agreement with the increased levels of COX-2 expression in chronic inflammatory disease (Morton & Dongari-Bagtzoglou 2001). In addition, macrophages predominated in the areawith inflammatory infiltrates as shown by a- ACT antibody. Thus, it is not surprising that increased levels of this enzyme were present in chronically inflamed radicular cyst tissue.
Radicular cysts are believed to result from continuous antigenic stimulation from inflamed or necrotic root canals. PG production as a result of COX-2 expression is an important factor in the pathogenesis of chronic inflammatory disorders. PGs have been implicated as mediators of bone destruction (Robinson et al. 1975). Since radicular cysts grow within the jaw bone, it is conceivable that expansion of cysts is accompanied by the growth of the cyst epithelium and is aided by the rate at which the surrounding bone is destroyed. Thus, one of the possible mechanisms of radicular cyst expansion in vivo may be via the COX-2 expression pathway.
In this study, COX-2 expression was found in radicular cysts. COX-2 is an inducible enzyme believed to be responsible for PG synthesis in inflammatory diseases. PG production as a result of COX-2 expression is an important factor in the pathogenesis of chronic inflammatory disorders. PGE2 has been implicated as a key mediator in the pathogenesis of pulpal diseases (Okiji et al. 1987, Okiji et al. 1989). In addition, PGE2 may play an important role in destruction of connective tissue matrix by triggering matrix metalloproteinase (MMP) secretion (Birkedal-Hansen 1993). Recently, evidence has demonstrated that MMPs play an important role in tissue destruction and disintegration of extracellular matrix in pulpal/periapical diseases (Oâ€™Boskey & Panagakos 1998). Epithelial cells from radicular cyst were found to secrete MMP-1 and -2 (Teronen et al. 1995). Recently, studies have also shown that bacterial products as well as proinflammatory cytokines can directly trigger pulp and periodontal ligament cells to express MMPs (Chang et al. 2001, Chang et al. 2002). Taken together, this may be partly explained by the fact that COX-2 is also a potent stimulator of MMP synthesis by resident cells resulting in tissue destruction and bone resorption during radicular cyst formation.
A previous study has demonstrated that proinflammatory cytokines are located in the lining epithelium, vascular endothelial cells and macrophages (Bando et al. 1993). Recently, proinflammatory cytokines and black pigmented Bacteroides were found to induce COX-2 expression in human pulp cells (Chang et al. 2003a,b, inpress).Therefore,COX-2activity in the lining epithelial and subepithelial connective tissue may be induced either directly by bacterial products from infected pulps or indirectly by inflammatory cytokines generated by epithelial cells. This might be the reason why COX-2plays an important role in radicular cyst development.
Immunolocalization of COX-2 was detected in the lining epithelium, subepithelial fibroblasts, macrophages and endothelial cells in all specimens. COX-2 expression may playanimportant role in the pathogenesis of radicular cysts. However, this studydoes not explain the immunomodulation during cyst development and growth. The role of COX-2 expression in the biological activity and/or activity of the radicular cyst should thoroughly be investigated in further studies.
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