Root canal contamination or exposure to lipopolysaccharide differentially modulate prostaglandin E 2 and leukotriene B 4 signaling in apical periodontitis

Abstract

Purpose: To evaluate the kinetics of apical periodontitis development in vivo, induced either by contamination of the root canals by microorganisms from the oral cavity or by inoculation of bacterial lipopolysaccharide (LPS) and the regulation of major enzymes and receptors involved in the arachidonic acid metabolism. Methodology: Apical periodontitis was induced in C57BL6 mice (n=96), by root canal exposure to oral cavity (n=48 teeth) or inoculation of LPS (10 µL of a suspension of 0.1 µg/µL) from E. coli into the root canals (n= 48 teeth). Healthy teeth were used as control (n=48 teeth). After 7, 14, 21 and 28 days the animals were euthanized and tissues removed for histopathological and qRT-PCR analyses. Histological analysis data were analyzed using two-way ANOVA followed by Sidak's test, and qRT-PCR data using two-way ANOVA followed by Tukey's test (α=0.05). Results: Contamination by microorganisms led to the development of apical periodontitis, characterized by the recruitment of inflammatory cells and bone tissue resorption, whereas inoculation of LPS induced inflammatory cells recruitment without bone resorption. Both stimuli induced mRNA expression for cyclooxygenase-2 and 5-lipoxygenase enzymes. Expression of prostaglandin E 2 and leukotriene B 4 cell surface receptors were more stimulated by LPS. Regarding nuclear peroxisome proliferator-activated receptors (PPAR), oral contamination induced the synthesis of mRNA for PPARδ, differently from inoculation of LPS, that induced PPARα and PPARγ expression. Conclusions: Contamination of the root canals by microorganisms from oral cavity induced the development of apical periodontitis differently than by inoculation with LPS, characterized by less bone loss than the first model. Regardless of the model used, it was found a local increase in the synthesis of mRNA for the enzymes 5-lipoxygenase and cyclooxygenase-2 of the arachidonic acid metabolism, as well as in the surface and nuclear receptors for the lipid mediators prostaglandin E2 and leukotriene B4.

Celecoxib treatment dampens LPS‐induced periapical bone resorption in a mouse model

“…2008, Paula‐Silva et al . 2009b, 2016, 2020, Cintra et al . 2014), but this analysis could be improved through radiographic and tomographic images as discussed elsewhere (Aksoy et al .…”

Targeting hepatocyte growth factor in epithelial–stromal interactions in an in vitro experimental model of human periodontitis

“…With regard to downregulated genes, we identified ANTXR2 and LAMA3, both being implicated in ECM interactions [ 43 , 44 ]. Further, leukotriene B4 receptor was also downregulated, suggesting a potential modification of the inflammatory status [ 45 , 46 ]. However, it needs to be stressed that the definite roles of the identified genes, being either down- or upregulated, remain to be determined with regard to their specific impact on periodontitis remodeling.…”

Oral Osteomicrobiology: The Role of Oral Microbiota in Alveolar Bone Homeostasis

“…However, the mechanisms by which the gut microbiota participate in bone regulation require further investigation. The oral cavity houses the second largest and second-most diverse microbiota after the gut in the body, with over 700 species of bacteria, fungi, viruses, archaea, and protozoa currently known (Paster et al, 2006). The alveolar bone is that part of the maxilla and mandible that supports the teeth, and the association of the oral microbiota with alveolar bone homeostasis has also received considerable attention (Costalonga and Herzberg, 2014;Hathaway-Schrader and Novince, 2021).…”

“…-3 g/L of LPS could directly stimulate bone loss, while a tiny concentration of LPS (10 -9 g/L) could indirectly promote bone loss by activating the production of bone resorptive cytokines and prostaglandins Paula-Silva et al, 2020;Beuscher et al, 1987;Tatakis et al, 1988. LPS could inhibit differentiation and proliferation while promoting apoptosis of osteoblasts via various mechanisms Wilson et al, 1988;Meghji et al, 1992;.…”