Periodontal disease is the most common osteolytic disease in humans and is significantly increased by diabetes mellitus. We tested the hypothesis that bacterial infection induces bone loss in diabetic animals through a mechanism that involves enhanced apoptosis. Type II diabetic rats were inoculated with Aggregatibacter actinomycetemcomitans and treated with a caspase-3 inhibitor, ZDEVD-FMK, or vehicle alone. Apoptotic cells were measured with TUNEL; osteoblasts and bone area were measured in H&E sections. New bone formation was assessed by labeling with fluorescent dyes and by osteocalcin mRNA levels. Osteoclast number, eroded bone surface, and new bone formation were measured by tartrate-resistant acid phosphatase staining. Immunohistochemistry was performed with an antibody against tumor necrosis factor-α. Bacterial infection doubled the number of tumor necrosis factor-α-expressing cells and increased apoptotic cells adjacent to bone 10-fold (P < 0.05). Treatment with caspase inhibitor blocked apoptosis, increased the number of osteoclasts, and eroded bone surface (P < 0.05); yet, inhibition of apoptosis resulted in significantly greater net bone area because of an increase in new bone formation, osteoblast numbers, and an increase in bone coupling. Thus, bacterial infection in diabetic rats stimulates periodontitis, in part through enhanced apoptosis of osteoblastic cells that reduces osseous coupling through a caspase-3-dependent mechanism.

Within the limits of this study, a 1% HA gel associated with a collagen scaffold can improve new bone formation in critical-size defects. However, this treatment never resulted in complete closure of the defects and healing in the major portion of the defects was characterized by fibrous tissue.

ABSTRACTThe purpose of this study was to test the hypothesis that diabetes aggravates periodontal destruction induced byAggregatibacter actinomycetemcomitansinfection. Thirty-eight diabetic and 33 normal rats were inoculated withA. actinomycetemcomitansand 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. AfterA. actinomycetemcomitansinfection, 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 byA. actinomycetemcomitansinfection in gingival epithelium and connective tissue (P< 0.05). These results provide new insight into how diabetes aggravatesA. 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.

As modern criteria for implant success have expanded to include parameters not only at the implant, peri-implant soft tissue and prosthesis levels, but also the patient's subjective evaluation, the planning and execution of implant rehabilitation in the anterior maxilla has become increasingly complex (Papaspyridakos, Chen, Singh, Weber, & Gallucci, 2012). In these cases, anterior implant treatment should satisfy the high aesthetic demands of the patient in order to obtain a result that best imitates the natural dentition. Prosthetically driven implant 3-D positioning is crucial and in order to optimize the aesthetic outcome and reduce the risk of post-operative bone loss and soft tissue recession, a minimum of 1.5 mm of BBT has been recommended (Monje et al., 2019). Numerous studies, however, have demonstrated a reduced thickness of the cortical bone in the anterior maxilla, with some reporting a high incidence of thin buccal

Aim To characterize the histologic and cellular response to A. actinomycetemcomitans (Aa) infection. Material and Methods Wistar rats infected with Aa were evaluated for antibody response, oral Aa colonization, loss of attachment, PMN recruitment, TNF-α in the junctional epithelium and connective tissue, osteoclasts, and adaptive immune response in local lymph nodes at baseline and 4, 5 or 6 weeks after infection. Some groups were given antibacterial treatment at 4 weeks. Results An antibody response against Aa occurred within 4 weeks of infection and 78% of inoculated rats had detectable Aa in the oral cavity (p<0.05). Aa infection significantly increased loss of attachment which was reversed by antibacterial treatment (p<0.05). TNF-α expression in the junctional epithelium followed the same pattern. Aa stimulated high osteoclast formation and TNF-α expression in the connective tissue (p<0.05). PMN recruitment significantly increased after Aa infection (p<0.05). Aa also increased the number of CD8+ T cells (p<0.05) but not CD4+ T cells or regulatory T cells (Tregs) (p>0.05). Conclusion Aa infection stimulated a local response which increased numbers of PMNs and TNF-α expression in the junctional epithelium and loss of attachment. Both TNF-a expression in JE and loss of attachment was reversed by antibiotic treatment. Aa infection also increased TNF-α in the connective tissue, osteoclast numbers, CD8+ T cells in lymph nodes. The results link Aa infection with important characteristics of periodontal destruction.