<i>Porphyromonas gingivalis</i>infection-induced tissue and bone transcriptional profiles

Meka, A.; Bakthavatchalu, Vasudevan; Sathishkumar, S.; López, María Cecilia; Verma, Raj Kumar; Wallet, Shannon M.; Bhattacharyya, Indraneel; Boyce, Brendan F.; Handfield, Martin; Lamont, Richard J.; Baker, Henry V.; Ebersole, Jeffrey L.; Kesavalu, Lakshmyya

doi:10.1111/j.2041-1014.2009.00555.x

Cited by 48 publications

(89 citation statements)

References 45 publications

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“…At the histological level, P. gingivalis infection induced bone loss, as reported previously (34). Interestingly, coinjection with miR-155 or anti-miR-2137 significantly decreased some aspects of the induced lesion, notably its size.…”

Section: Gingivalis (Pg) (A To C) Combination (P Gingivalis and Mirsupporting

confidence: 84%

Identification and Characterization of MicroRNA Differentially Expressed in Macrophages Exposed to Porphyromonas gingivalis Infection

et al. 2017

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MicroRNAs (miRNAs) are short, noncoding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert any innate immune response. In this study we analyzed, using microarray analysis, the bacterial modulation of miRNAs in bone marrow-derived macrophages (BMMs) in which activity was induced by infection with Porphyromonas gingivalis. The expression of several miRNAs was modulated 3 h postinfection (at a multiplicity of infection of 25). A bioinformatic analysis was performed to further identify pathways related to the innate immune host response under the influence of selected miRNAs. To assess the effects of the miRNAs identified on cytokine secretion (tumor necrosis factor alpha [TNF-␣] and interleukin-10 [IL-10]), BMMs were transfected with selected miRNA mimics and inhibitors. Transfection with mmu-miR-155 and mmumiR-2137 did not modify TNF-␣ secretion, while their inhibitors increased it. Inhibitors of mmu-miR-2137 and mmu-miR-7674 increased the secretion of the anti-inflammatory factor IL-10. In P. gingivalis-infected BMMs, mmu-miR-155-5p significantly decreased TNF-␣ secretion while inhibitor of mmu-miR-2137 increased IL-10 secretion. In vivo, in a mouse model of P. gingivalis-induced calvarial bone resorption, injection of mmu-miR-155-5p or anti-mmu-miR-2137 reduced the size of the lesion significantly. Furthermore, anti-mmu-miR-2137 significantly reduced inflammatory cell infiltration, osteoclast activity, and bone loss. Bioinformatic analysis demonstrated that pathways related to cytokine-and chemokinerelated pathways but also osteoclast differentiation may be involved in the effects observed. This study contributes further to our understanding of P. gingivalis-induced modulation of miRNAs and their physiological effects. It highlights the potential therapeutic merits of targeting mmu-miR-155-5p and mmumiR-2137 to control inflammation induced by P. gingivalis infection.

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Section: Gingivalis (Pg) (A To C) Combination (P Gingivalis and Mirsupporting

confidence: 84%

Identification and Characterization of MicroRNA Differentially Expressed in Macrophages Exposed to Porphyromonas gingivalis Infection

et al. 2017

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“…A buccal gingival sample from either healthy or periodontitis‐affected tissue from the premolar/molar maxillary region of each animal was taken using a standard gingivectomy technique, and maintained frozen in RNAlater solution. Total RNA was isolated from each gingival tissue using a standard procedure as we have described and tissue RNA samples were submitted to the microarray core to assess RNA quality and analyse the transcriptome using the GeneChip ® Rhesus Macaque Genome Array (Affymetrix, Santa Clara, CA) . Individual samples were used for gene expression analyses.…”

Section: Methodsmentioning

confidence: 99%

Hypoxia‐inducible transcription factors, HIF1A and HIF2A, increase in aging mucosal tissues

et al. 2018

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Hypoxia (i.e. oxygen deprivation) activates the hypoxia-signalling pathway, primarily via hypoxia-inducible transcription factors (HIF) for numerous target genes, which mediate angiogenesis, metabolism and coagulation, among other processes to try to replenish tissues with blood and oxygen. Hypoxia signalling dysregulation also commonly occurs during chronic inflammation. We sampled gingival tissues from rhesus monkeys (Macaca mulatta; 3-25 years old) and total RNA was isolated for microarray analysis. HIF1A, HIF1B and HIF2A were significantly different in healthy aged tissues, and both HIF1A and HIF3A were positively correlated with aging. Beyond these transcription factor alterations, analysis of patterns of gene expression involved in hypoxic changes in tissues showed specific increases in metabolic pathway hypoxia-inducible genes, whereas angiogenesis pathway gene changes were more variable in healthy aging tissues across the animals. With periodontitis, aging tissues showed decreases in metabolic gene expression related to carbohydrate/lipid utilization (GBE1, PGAP1, TPI1), energy metabolism and cell cycle regulation (IER3, CCNG2, PER1), with up-regulation of transcription genes and cellular proliferation genes (FOS, EGR1, MET, JMJD6) that are hypoxia-inducible. The potential clinical implications of these results are related to the epidemiological findings of increased susceptibility and expression of periodontitis with aging. More specifically the findings describe that hypoxic stress may exist in aging gingival tissues before documentation of clinical changes of periodontitis and, so, may provide an explanatory molecular risk factor for an elevated capacity of the tissues to express destructive processes in response to changes in the microbial biofilms characteristic of a more pathogenic microbial challenge.

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“…Total RNA was isolated from each gingival tissue using a standard procedure as we have described and tissue RNA samples submitted to the microarray core to assess RNA quality analyze the transcriptome using the GeneChip® Rhesus Macaque Genome Array (Affymetrix) (16, 22). Individual samples were used for gene expression analyses.…”

Section: Methodsmentioning

confidence: 99%

Immune system transcriptome in gingival tissues of young nonhuman primates

González

Nagarajan

Novak

et al. 2015

J of Periodontal Research

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Young/adolescent humans demonstrate many microorganisms associated with periodontal disease in adults and substantial gingival inflammatory responses. However, younger individuals do not demonstrate the soft and hard tissue destruction that hallmark periodontitis. This study evaluated responses to the oral microbial ecology in gingival tissues from clinically healthy young Macaca mulatta (<3 years old) compared to older animals (5-23 years old). Global transcriptional profiling of four age groups revealed a subset of 159 genes that were differentially expressed at least across one of the age comparisons. Correlation metrics generated a relevance network abstraction of these genes. Partitioning of the relevance network revealed seven distinct communities comprising functionally related genes associated with host inflammatory and immune responses. A group of genes were identified that were selectively increased/decreased or positively/negatively correlated with gingival profiles in the animals. A Principal Components Analysis created metagenes of expression profiles for classifying the 23 animals. The results provide novel system-level insights into gene expression differences in healthy young tissues weighted towards host responses that were associated with anti-inflammatory biomolecules or those linked with T cell regulation of responses. The combination of the regulated microenvironment may help to explain the apparent “resistance” of younger individuals to developing periodontal disease.

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Porphyromonas gingivalisinfection-induced tissue and bone transcriptional profiles

Cited by 48 publications

References 45 publications

Identification and Characterization of MicroRNA Differentially Expressed in Macrophages Exposed to Porphyromonas gingivalis Infection

Identification and Characterization of MicroRNA Differentially Expressed in Macrophages Exposed to Porphyromonas gingivalis Infection

Hypoxia‐inducible transcription factors, HIF1A and HIF2A, increase in aging mucosal tissues

Immune system transcriptome in gingival tissues of young nonhuman primates

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