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Role of the Activation of the Nuclear Enzyme Poly(ADP-Ribose) Polymerase in the Pathogenesis of Periodontitis

¹ Institute of Human Physiology and Clinical Experimental Research, and ² Department of Anatomy, Semmelweis University, 78/A Üllöi út, Budapest, Hungary, 1082; and ³ Inotek Pharmaceuticals Corporation, Beverly, MA, USA;

View larger version (57K): [in a new window]   Figure 1. Evidence for poly(ADP-ribose) polymerase (PARP) activation in periodontitis. Immunohistochemical staining of rat gingivomucosal tissue for poly(ADP-ribose) formation, an indicator PARP activation, in healthy control (a), experimental periodontitis (b), and PARP inhibitor PJ34-treated experimental periodontitis (c). Bars = 100 µm. (a) In the gingivomucosal tissue of the control side, only a few poly(ADP-ribose) immunopositive nuclei (arrow) were found in the connective tissue. [The connective tissue-epithelium (E) interfaces are marked by arrowheads.] (b) In the ligated side, there are large numbers of strongly poly(ADP-ribose) immunoreactive nuclei in the subepithelial connective tissue. [The arrowheads indicate the connective tissue-epithelium (E) border.] (c) Treatment with PJ34 attenuated PARP activation in the gingivomucosal tissue of the ligated side (arrows). [The connective tissue-epithelium (E) interfaces are marked by arrowheads.]

View larger version (110K): [in a new window]   Figure 2. Photomicrographs of the poly(ADP-ribose) immunoreactive nuclei in rat gingivomucosal tissue in periodontitis. Bars = 50 µm (a,b,f) and 25 µm (c,d,e,g). (a) In the higher magnification of the connective tissue of the ligated animal, the thick arrow indicates the nuclei of fibroblasts, the arrowhead shows the nucleus of an eosinophil granulocyte, and the small arrow indicates a reactive endothelial cell of a capillary (C). (b) Thick arrows show the immunoreactive segmented nuclei of neutrophil granulocytes. (c) In the higher magnification of the connective tissue of the ligated animal, the thick arrow indicates the stained nucleus of an eosinophil granulocyte, and the arrowhead shows a monocyte. (d) The thick arrow marks the elliptical nucleus of a fibroblast, and the arrowhead indicates a mast cell having an immunoreactive nucleus. (e) Reactive smaller round nucleus of a lymphocyte is shown by a thick arrow; arrowhead indicates an immunonegative nucleus of a mast cell. (f) Longitudinal section of a capillary (C) with immunoreactive endothelial nuclei (arrowheads). (g) Cross-section of a vessel (V) where the immunopositive endothelial nuclei are marked by arrowheads.

View larger version (26K): [in a new window]   Figure 3. The effect of PARP inhibitor PJ34 on vascular permeability of gingivomucosal tissue (upper panel) and on alveolar bone destruction at the mediolingual root (lower panel) in ligature-induced periodontitis in the rat. Data are mean + SEM; n = 9 in both groups. a, significantly different (p < 0.05) from the contralateral side (non-ligated right side); b, significantly different (p < 0.05) from control (vehicle treatment).

View larger version (44K): [in a new window]   Figure 4. The effect of genetic PARP deficiency on vascular permeability of gingivomucosal tissue (upper panel) and on alveolar bone destruction at the distal root (lower panel) in ligature-induced periodontitis in mice. Data are mean + SEM; n = 8 in both groups. a, significantly different (p < 0.05) from the contralateral side (non-ligated right side); b, significantly different (p < 0.05) from control (wild-type).