Reactive Change in Proliferative Activity of the Junctional Epithelium After Topical Application of Lipopolysaccharide

Abstract

IT IS WELL ESTABLISHED THAT apical migration of junctional epithelium (JE) along a root surface is an important factor in periodontal pocket formation and deepening. However, the exact mechanism and, more specifically, the role of inflammatory products in influencing the activity of cells within the JE is not known. To address this issue lipopolysaccharide (LPS) was applied topically into rat molar gingival sulcus and then tissues evaluated immunohistochemically for expression of proliferating cell nuclear antigen (PCNA). Tissues were prepared for histological analysis at designated times. Histologically, infiltration of neutrophils with associated edema was noted in JE and gingival connective tissues 6 hours after LPS application and was prominent at 12 hours. These inflammatory changes persisted in the 2- and 3-day specimens, and disappeared at 5 days. In normal gingiva, before the LPS application, the JE showed few PCNA positive cells, while almost all cells in the basal and suprabasal cell layers of the oral gingival epithelium and the oral sulcular epithelium were PCNA positive. No increase in the number of PCNA positive cells in the JE beyond zero time was observed at 6 and 12 hours after LPS application. One day after LPS application, PCNA positive cells appeared in the basal cell layer of the JE, with a continued increase number of PCNA positive cells in the JE continued at 2 and 3 days. By day 5 the number of PCNA positive cells were decreasing with return to a normal range by 7 days. These results showed that 1) under normal physiological conditions, cells within the JE have minimal mitotic activity and 2) the JE cells can enter the proliferating cell cycle when exposed to LPS, and suggest that the enhanced proliferating activity in the JE is an important factor for the deepening of the periodontal pocket, if the connective tissue attachment is broken down.

Inhibitory effects of orally administrated liposomal bovine lactoferrin on the LPS-induced osteoclastogenesis

“…32 In addition, periodontal tissue destruction caused by topical application of E. coli LPS into the rat gingival sulcus is well established. [7][8][9][10][11] In our animal model, typical B-cell lesion-like human chronic periodontitis did not develop. However, it has been well accepted that periodontal tissue destruction progresses by recurrent acute episodes.…”

“…[3][4][5] It is well demonstrated that these proinflammatory cytokines having bone resorbing activity, act osteoblasts (OBs) and stimulate osteoclastogenesis through upregulation of receptor activator of NFkB (RANKL) and downregulation of osteoprotegerin (OPG) in OBs. 6 Earlier, we have reported that initial periodontal tissue damage was provoked by topical application of Escherichia coli LPS into the rat gingival sulcus; infiltration of numerous polymorphonuclear leucocytes in the junctional epithelium (JE), 7 transient accumulation of exudative macrophages, 8 vascular dilatation and inflammatory edema in the sub-JE, enhancement of proliferative activity of JE cells, 9 and stimulation of osteoclastic bone resorption. 7 Furthermore, using this animal model, we have shown upregulation of immunoexpression of TNF-a, IL-1b, 10 and chemokines 11 in periodontal tissue and suggested that transiently produced cytokines from the host cells may be involved in the initiation of inflammation and subsequent periodontal tissue destruction.…”

Absence of αvβ6 Integrin Is Linked to Initiation and Progression of Periodontal Disease

“…To investigate whether the changes observed in Itgb6 Ϫ/Ϫ mice were caused by altered TGF-␤1 signaling, we used a rat model, 39,40 in which the early signs of periodontal disease can be initiated in a relatively short period of time, to block the ␣v␤6 integrin-mediated TGF-␤1 activation by a specific antibody. Ligatures have been extensively used for creation of periodontal defects, mainly for studies aimed at therapeutical interventions.…”

Induction of Keratinocyte Growth Factor 1 Expression by Lipopolysaccharide Is Regulated by CD-14 and Toll-Like Receptors 2 and 4

“…Proliferation and invasion of junctional and sulcular epithelium into the connective tissue starts early in the disease process and may continue to ultimately form a periodontal pocket (33). Topical application of purified Escherichia coli LPS to the rat molar gingival sulcus induced significant junctional epithelial basal cell proliferation (46). Regulation of junctional epithelial cell proliferation may occur either directly or indirectly.…”

“…Second, we examined the signaling pathway that mediates E. coli LPS stimulation of KGF-1 mRNA and protein expression. LPS purified from E. coli has been extensively used to study cellular responses in several in vitro and in vivo periodontal pathogenesis investigations (44,46,52), and we previously established that LPSs purified from P. gingivalis and E. coli both induced the same qualitative increase in KGF-1 protein expression (40).…”