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.

ObjectivesTo perform a comprehensive and integrative review of the available literature on the potential changes in the microbiome of healthy and individuals with diabetes under periodontal health and disease.Materials and MethodsThe review was conducted by two independent reviewers. Indexed electronic databases (PubMed/Medline, Cochrane Library, Web of Science and Scopus) were searched, including articles published in English and dated from 5 years ago until December 2021. A manual search also was performed to identify co-related articles. Following the removal of duplicates and eligibility criteria, the articles were included in tables for analysis and described in the manuscript.ResultsAccording to this review, diabetes mellitus was associated with significant changes in the subgingival and salivary microbiome, either in its association with periodontitis or in cases of periodontal health. In addition to affecting microbial diversity in terms of taxonomy, metagenomic studies have shown that this endocrine disorder may also be directly related to increased pathogenicity in the oral microbiome.ConclusionAlthough the reviewed studies demonstrate important differences in the subgingival and salivary microbiome composition because of diabetes mellitus, further studies are needed to clarify the real effects of hyperglycemia on oral microbial profiles and support new diagnostic approaches and innovative treatments.

Thyroid hormones may influence the healing process in the cortical bone around titanium implants placed in rats, whereas cancellous bone seems to be less sensitive to changes in T(3) and T(4) serum levels.

Periodontitis is a chronic inflammatory condition initiated by the accumulation of bacterial biofilm. It is highly prevalent and when left untreated can lead to tooth loss. The presence of bacterial biofilm is essential for the initiation of the inflammatory response but is not the sole initiator. Currently it is unknown which mechanisms drive the dysbiosis of the bacterial biofilm leading to the dysregulation of the inflammatory response. Other players in this equation include environmental, systemic, and genetic factors which can play a role in exacerbating the inflammatory response. Treatment of periodontal disease consists of removal of the bacterial biofilm with the goal of resolving the inflammatory response; however, this does not occur in every case. Understanding the way the inflammatory response does not return to a state of homeostasis has led investigators to consider both systemic and local pharmacological interventions. Nonetheless, a better understanding of the impact that genetics and environmental factors may have on the inflammatory response could be key to helping identify how inflammation can be modulated therefore stopping the destruction of the periodontium. In this article, we will explore the current evidence associating the microbial dysbiosis and the dysregulation of the immune response, potential mechanisms or pathways that may be targeted for the modulation of the inflammatory response, and discuss the advantages and drawbacks associated with local and systemic inflammatory modulation in the management of periodontal disease. This information will be valuable for those interested in understanding potential adjunct methods for managing periodontal diseases, but not limited to, dental professionals, clinical researchers and the public at large.