PDGF‐B Producing Cells and PDGF‐B Gene Expression in Normal Gingiva and Cyclosporine A‐Induced Gingival Overgrowth

Abstract

It has been proposed that healthy gingiva is in a continuous state of wound repair. Thus, one might expect to find cells in normal gingiva producing growth factors associated with wound healing such as platelet-derived growth factor B chain (PDGF-B). One might also expect to find increased numbers of these cells or increased amounts of these growth factors in conditions which involve increased tissue volume such as drug-induced gingival overgrowth (DGO). The purpose of this study was to quantify PDGF-B gene expression and identify cells producing PDGF-B in normal gingiva and DGO. Cyclosporine A (CSA) was selected as a prototype of the overgrowth condition. Twelve patients with clinical CSA DGO and 12 patients with no DGO or history of drugs known to cause DGO were selected for study. Frozen sections of gingival specimens from these patients were subjected to in situ hybridization for PDGF-B mRNA. Positive cells were counted and expressed as mean +/- SEM cells/mm2 of lamina propria. Morphometric analysis revealed 6.2 +/- 1.9 cells/mm2 for control gingiva and 10.3 +/- 3.4 cells/mm2 for CSA DGO samples. There was no statistically significant difference between groups. PDGF-B gene expression was measured in these cells and expressed as mean +/- SEM silver grains/cells. There was a significant upregulation of PDGF-B gene expression in cells from the CSA DGO group (39.5 +/- 14.7 silver grains/cell for normal gingiva vs. 255.3 +/- 77.1 silver grains/cell for CSA DGO samples; P < 0.001). The presence of PDGF-B in these cells was confirmed in all cases by immunocytochemical localization. Additionally, PDGF-B producing cells were identified as macrophages in sections taken from an additional patient with CSA DGO by double immunofluorescence labeling of the CD51 membrane marker for macrophages and intracellular PDGF-B. These findings are consistent with the concept that healthy gingiva is in a continuous state of wound repair and support the hypothesis that CSA DGO is associated with enhanced macrophage PDGF-B gene expression rather than an increase in the number of PDGF-B producing macrophages.

In vivo association of immunophenotyped macrophages expressing CD163 with PDGF-B in gingival overgrowth-induced by three different categories of medications

“…37 The present study showed elevated expression PDGF-B in groups II compared to groups III and IV. This observation is convenient with Plemons et al 38 who found that healthy gingiva is in a continuous state of wound repair and support the hypothesis that CSA-induced GO is associated with enhanced macrophage PDGF-B gene expression rather than an increase in the number of PDGF-B producing macrophages. In addition, Dill et al 36 analyzed RNA isolated from GO associated with CsA and PNT and reported that expression of PDGF gene was 47-fold greater than control.…”

Connective Tissue Metabolism and Gingival Overgrowth

“…In contrast, macrophages in highly inflamed tissues express predominantly the 27E10 marker . Even though IL-1␤ levels have not been shown to be increased in cyclosporin-A-treated monocytes/macrophages, there was a significant up-regulation in PDGF-B in response to cyclosporin A and phenytoin (Plemons et al, 1996;Iacopino et al, 1997). Similarly, phenytoin, cyclosporin A, and nifedipine gingival overgrowth tissues contain subpopulations of macrophages and other inflammatory cells that differ from those in healthy control gingival tissues (Dahllof et al, 1985;Pernu et al, 1994;Cebeci et al, 1996Cebeci et al, , 1998Pernu and Knuuttila, 2001;Bulut et al, 2002;Echelard et al, 2002).…”

Healing following tooth extraction in cyclosporine-fed rats

“…To understand the processes responsible for induction of gingival overgrowth, researchers have studied the effects of CSA on gingival cell metabolism 6,18,23 . However, relatively little attention has focused on the effects of CSA on the oral hard tissue, the tooth and the surrounding bony tissue.…”