title: Aggregatibacter actinomycetemcomitans infection enhances apoptosis in vivo through a caspase-3-dependent mechanism in experimental periodontitis.
abstract: The purpose of this study was to test the hypothesis that diabetes aggravates periodontal destruction induced by Aggregatibacter actinomycetemcomitans infection. Thirty-eight diabetic and 33 normal rats were inoculated with A. actinomycetemcomitans and euthanized at baseline and at 4, 5, and 6 weeks after inoculation. Bone loss and the infiltration of polymorphonuclear leukocytes (PMNs) in gingival epithelium were measured in hematoxylin-eosin-stained sections. The induction of tumor necrosis factor alpha (TNF-α) was evaluated by immunohistochemistry and of apoptotic cells by a TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay. After A. actinomycetemcomitans infection, the bone loss in diabetic rats was 1.7-fold and the PMN infiltration 1.6-fold higher than in normoglycemic rats (P < 0.05). The induction of TNF-α was 1.5-fold higher and of apoptotic cells was up to 3-fold higher in diabetic versus normoglycemic rats (P < 0.05). Treatment with a caspase-3 inhibitor significantly blocked noninflammatory cell apoptosis induced by A. actinomycetemcomitans infection in gingival epithelium and connective tissue (P < 0.05). These results provide new insight into how diabetes aggravates A. actinomycetemcomitans-induced periodontal destruction in rats by significantly increasing the inflammatory response, leading to increased bone loss and enhancing apoptosis of gingival epithelial and connective tissue cells through a caspase-3-dependent mechanism. Antibiotics had a more pronounced effect on many of these parameters in diabetic than in normoglycemic rats, suggesting a deficiency in the capacity of diabetic animals to resist infection.
authors.affiliation: Department of Periodontology, School and Hospital of Stomatology, Peking University, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Kang
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Brito Bezerra
authors.forename: Sandra
authors.initials: S
authors.lastname: Pacios
authors.forename: Oelisoa
authors.initials: O
authors.lastname: Andriankaja
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Vincent
authors.initials: V
authors.lastname: Tsiagbe
authors.forename: Helen
authors.initials: H
authors.lastname: Schreiner
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fine
authors.forename: Dana T
authors.initials: DT
authors.lastname: Graves
mesh_terms: D000189:Actinobacillus Infections / Q000473:pathology*; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000907:Antibodies, Bacterial / Q000097:blood; D017209:Apoptosis; D001422:Bacterial Adhesion; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D007074:Immunoglobulin G / Q000097:blood; D010518:Periodontitis / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D061945:Caspase Inhibitors; D007074:Immunoglobulin G; C505410:Casp3 protein, rat; D053148:Caspase 3