Kenza Saadi-Thiers’s research while affiliated with University of Strasbourg and other places

Background: The great variability of periodontal and systemic responses to experimental periodontitis reflects the inherent pathogenic complexity of mice models and could limit the resulting interpretations and their extension to human diseases. This study compared the effect of Porphyromonas gingivalis (Pg) infection and experimental periodontitis duration at local and systemic levels in various models. Methods: Periodontitis was induced in C57BL/6J mice by ligatures previously incubated with Pg (LIGPG group) or not (LIG group) or by oral gavage (GAV) with Pg ATCC 33277. Blood samples were taken, and mice were euthanized at different times. Periodontal tissue destruction, osteoclast number, and inflammation were assessed by histomorphometry, tartrate-resistant acid phosphatase histoenzymology, and cathepsin B (CATB) and matrix metalloproteinase 9 (MMP9) immunochemistry. Serum levels of interleukin-6 (IL-6) and IL-1β were measured using enzyme-linked immunosorbent assay bioplex methods. Results: Periodontal tissue destruction and osteoclast numbers were significantly elevated in LIGPG models compared to LIG and GAV models. They increased with time with the exception of osteoclast numbers in the LIG model. CATB and MMP9 expression was related to bone destruction processes and Pg infection. The highest serum levels of IL-6 and IL-1β were observed in the LIGPG group. A decrease of IL-6 and an increase of IL-1β serum level were observed with time in LIGPG group contrary to LIG group. Conclusions: These data indicate that Pg infection worsened periodontal tissue destruction through specific pathogenic pathways and modified systemic response to periodontal inflammation. Furthermore, the blood cytokine response to ligature models showed their relevance for evaluating the systemic impact of periodontal disease.

Objectives: Clinical studies have recently shown that periodontal diseases, especially severe periodontitis, worsened atherosclerosis. This influence could be explain by direct effects of periodontal pathogens (Porphyromonas gingivalis - PG) on vessel walls, and/or increased levels of systemic pro-inflammatory cytokines (IL-6, TNFalpha). Previous in vitro investigations have shown that PG triggers deleterious inflammatory responses of both gingival and endothelial cells. This study aimed to evaluate in vivo the specific responses to PG infection at local and systemic level in various experimental periodontitis models. Methods: Severe periodontitis were induced in C57BL/6J mice by wrapping silk ligatures previously incubated (LIGPG group) or not (LIG group) with PG around first maxillary molars and compared to a mice control group. Blood samples were taken and mice were euthanized on days 15, 30 and 45 after ligature placement. Periodontal tissue destruction and inflammation were evaluated by histomorphometry and osteoclast TRAP enzymohistochemistry. Serum level of IL-6 and TNFalpha were measured by using ELISA bioplex methods (Bioplex, BioRad). Results: The results showed that loss of connective attachment is higher in LIGPG mice compared to LIG mice at 15 days. The number of osteoclasts was significantly (p<0.05) higher in LIGPG mice compared to LG mice. At 15 days, the serum levels of IL-6 (p=0.05) and TNFalpha (p<0.01) were significantly increased in the LIGPG group compared the control group. Furthermore, serum level of Il-6 was also higher (twice) in the LIGPG group than in the LIG group. At 30 and 45 days, serum level of IL-6 was lower in the LIGPG than in the other groups. Conclusion: The data confirmed the specific pathogenic role of PG in periodontal inflammation and showed the reliability of our model to investigate the periodontitis systemic influence. Indeed, the initial/acute phase of PG infection was associated to a systemic increase of pro-inflammatory cytokines.

Cardiovascular disease, such as atherosclerosis, is the main cause of mortality in developed countries. Most atherosclerosis risk factors have been identified and are treated, improving patient cardiovascular status and reducing mortality, but some remain unknown. Periodontal disease is generally defined as inflammatory disease initiated by accumulation of dental bacterial plaque, leading to the destruction of tissues that support the teeth. Severe forms have a high prevalence (15% of the population) and are associated with the presence of virulent pathogens such as Porphyromonas gingivalis. Epidemiological studies have shown that severe periodontal disease negatively influences cardiovascular status. The aim of this paper was to present a synthesis of the most recent biological data related to the link between periodontal and cardiovascular disease. The potential biological mechanisms involved in these two inflammatory diseases (bacteriological theory, inflammatory theory, immune theory) were developed. According to the observed positive effects of periodontal treatment on systemic conditions, the benefit of a reinforced collaboration between dentists and cardiologists was discussed, especially for patients at risk for cardiovascular disease.