Dataset Information

Quantitative gene expression profiling implicates genes for susceptibility and resistance to alveolar bone loss.

ABSTRACT: Periodontal disease is one of the most prevalent chronic inflammatory diseases. There is a genetic component to susceptibility and resistance to this disease. Using a mouse model, we investigated the progression of alveolar bone loss by gene expression profiling of susceptible and resistant mouse strains (BALB/cByJ and A/J, respectively). We employed a novel and sensitive quantitative real-time PCR method to compare basal RNA transcription of a 48-gene set in the gingiva and the spleen and the subsequent changes in gene expression due to Porphyromonas gingivalis oral infection. Basal expression of interleukin-1 beta (Il1b) and tumor necrosis factor alpha (Tnf) mRNA was higher in the gingiva of the susceptible BALB/cByJ mice than in the gingiva of resistant A/J mice. Gingival Il1b gene expression increased further and Stat6 gene expression was turned on after P. gingivalis infection in BALB/cByJ mice but not in A/J mice. The basal expression of interleukin-15 (Il15) in the gingiva and the basal expression of p-selectin (Selp) in the spleen were higher in the resistant A/J mice than in the susceptible BALB/cByJ mice. In the resistant A/J mice the expression of no genes detectably changed in the gingiva after infection. These results suggest a molecular phenotype in which discrete sets of differentially expressed genes are associated with genetically determined susceptibility (Il1b, Tnf, and Stat6) or resistance (Il15 and Selp) to alveolar bone loss, providing insight into the genetic etiology of this complex disease.

SUBMITTER: Hart GT

PROVIDER: S-EPMC470695 | biostudies-literature | 2004 Aug

REPOSITORIES: biostudies-literature

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Quantitative gene expression profiling implicates genes for susceptibility and resistance to alveolar bone loss.

Hart G T GT Shaffer D J DJ Akilesh S S Brown A C AC Moran L L Roopenian D C DC Baker P J PJ

Infection and immunity 20040801 8

Periodontal disease is one of the most prevalent chronic inflammatory diseases. There is a genetic component to susceptibility and resistance to this disease. Using a mouse model, we investigated the progression of alveolar bone loss by gene expression profiling of susceptible and resistant mouse strains (BALB/cByJ and A/J, respectively). We employed a novel and sensitive quantitative real-time PCR method to compare basal RNA transcription of a 48-gene set in the gingiva and the spleen and the s ...[more]

PMID: 15271905

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Project description:Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses. The study purpose was to determine whether antimicrobial-induced disruption of the commensal microbiota has deleterious effects on alveolar bone. We administered an antibiotic cocktail, minocycline, or vehicle-control to sex-matched C57BL/6T mice from age 6- to 12 weeks. Antibiotic cocktail and minocycline had catabolic effects on alveolar bone in specific-pathogen-free (SPF) mice. We then administered minocycline or vehicle-control to male mice reared under SPF and germ-free conditions, and we subjected minocycline-treated SPF mice to chlorhexidine oral antiseptic rinses. Alveolar bone loss was greater in vehicle-treated SPF versus germ-free mice, demonstrating that the commensal microbiota drives naturally occurring alveolar bone loss. Minocycline- versus vehicle-treated germ-free mice had similar alveolar bone loss outcomes, implying that antimicrobial-driven alveolar bone loss is microbiota dependent. Minocycline induced phylum-level shifts in the oral bacteriome and exacerbated naturally occurring alveolar bone loss in SPF mice. Chlorhexidine further disrupted the oral bacteriome and worsened alveolar bone loss in minocycline-treated SPF mice, validating that antimicrobial-induced oral dysbiosis has deleterious effects on alveolar bone. Minocycline enhanced osteoclast size and interface with alveolar bone in SPF mice. Neutrophils and plasmacytoid dendritic cells were upregulated in cervical lymph nodes of minocycline-treated SPF mice. Paralleling the upregulated proinflammatory innate immune cells, minocycline therapy increased TH 1 and TH 17 cells that have known pro-osteoclastic actions in the alveolar bone. This report reveals that antimicrobial perturbation of the commensal microbiota induces a proinflammatory oral dysbiotic state that exacerbates naturally occurring alveolar bone loss.

Dataset Information

Quantitative gene expression profiling implicates genes for susceptibility and resistance to alveolar bone loss.

Publications

Quantitative gene expression profiling implicates genes for susceptibility and resistance to alveolar bone loss.

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