Molecular characterization of Treponema denticola infection-induced bone and soft tissue transcriptional profiles

Abstract

SUMMARYTreponema denticola is associated with subgingival biofilms in adult periodontitis and with acute necrotizing ulcerative gingivitis. However, the molecular mechanisms by which T. denticola impacts periodontal inflammation and alveolar bone resorption remain unclear. Here, we examined changes in the host transcriptional profiles during a T. denticola infection using a murine calvarial model of inflammation and bone resorption. T. denticola was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and the calvarial bones were excised. RNA was isolated and analysed for transcript profiling using Murine GeneChip® arrays. Following T. denticola infection, 2905 and 1234 genes in the infected calvarial bones and soft tissues, respectively, were differentially expressed (p ≤ 0.05). Biological pathways significantly impacted by T. denticola infection in calvarial bone and calvarial tissue included leukocyte transendothelial migration, cell adhesion (immune system) molecules, cell cycle, extracellular matrix-receptor interaction, focal adhesion, B-cell receptor signaling and transforming growth factor-β signaling pathways resulting in proinflammatory, chemotactic effects, and T-cell stimulation. In conclusion, localized T. denticola infection differentially induces transcription of a broad array of host genes, the profiles of which differed between inflamed calvarial bone and soft tissues.

Periodontal microbial complexes associated with specific cell and tissue responses

“…Importantly, the observed transcriptional profiles differed between soft and hard tissue, underscoring the need to study separately the individual tissue components in order to dissect the molecular mechanisms involved in the host response to the bacterial challenge. A recent study of T. denticola subcutaneous injections by the same group showed similar results (Bakthavatchalu et al 2010). Unfortunately, no comparisons of the tissue‐specific responses following infection by each of the two pathogens were reported.…”

Animal Models to Study Host-Bacteria Interactions Involved in Periodontitis

“…In one example, P. gingivalis, T. denticola and T. forsythia were injected into the connective tissue overlying calvarial bone in mice, and mRNA profiling was performed. This led to the identification of a number of inflammatory mediators that were induced in a bacteria-specific pattern [79–81]. …”

“…The microarray studies mentioned above indicated that the gene transcription profiles in inflamed calvarial bone induced by microbial infection were different from the profiles observed in the soft tissue [79–81]. Another study has demonstrated the use of this model to examine a bacterially induced soft tissue wound that follows the classic steps of healing, including the migration of fibroblasts into the wounded site, proliferation, production of extracellular matrix and reorganization [85].…”

Invasion of Oral and Aortic Tissues by Oral Spirochete Treponema denticola in ApoE −/− Mice Causally Links Periodontal Disease and Atherosclerosis

“…In a murine calvarial model of inflammation, bone resorption was characterized by distinct host transcriptional profiles (12) (inflammatory mediators, cell adhesion, extracellular matrix [ECM] interactions, and cell cycle components) that demonstrate the acute pathogenicity of T. denticola. These features of aggressive oral pathology have been reported to correlate with the detection of T. denticola aggregated antigenic particles in human atherosclerotic lesions (13) in carotid arterial specimens and atheromatous plaques by fluorescent in situ hybridization (FISH) (14); however, a direct causative relation has not been proven.…”