title: Ligature-induced periodontitis in mice induces elevated levels of circulating interleukin-6 but shows only weak effects on adipose and liver tissues.
abstract: OBJECTIVE
  Our previous study demonstrated using an oral gavage model that Porphyromonas gingivalis could induce various inflammatory changes linked to periodontitis-associated systemic diseases by altering gut microbiota. A ligature-induced periodontitis model is similar to human periodontitis in various aspects: in both cases, alveolar bone resorption depends on oral bacterial load, and gingival tissue becomes infiltrated with inflammatory cells. Therefore, this model may be suitable for the analysis of bacterial burden and gingival tissue inflammation with changes related to systemic diseases.
  
  
  METHODS
  Periodontal tissue destruction was induced by a 2 wk ligature placement around the bilateral maxillary second molar. We analyzed the expression profile of various genes in several tissues, levels of systemic inflammatory markers and induction of insulin resistance. In addition, we studied changes in gut microbiota composition and bacterial load in the oral cavity.
  
  
  RESULTS
  Two weeks after ligature placement gingival inflammation was significantly induced with a disrupted gingival epithelial barrier and alveolar bone resorption accompanied by increased bacterial burden in the oral cavity. Gene expression analysis of the gingival tissue of ligated mice demonstrated that interleukin (Il)1b was significantly elevated and Il6 and Il17a tended to be higher in ligated mice than in untreated mice. Although serum IL-6 was significantly elevated and serum amyloid A tended to be higher in ligated compared to untreated mice, endotoxin levels did not differ between the two groups. Among the genes whose expressions are closely related to glucose and lipid metabolisms, only phosphoenolpyruvate carboxykinase 1 (Pck1) and acetyl-coenzyme A carboxylase alpha (Acaca) showed significant changes following ligature placement in the liver, with the former upregulated and the latter downregulated. However, insulin sensitivity did not change following ligature placement. Furthermore, ligature placement weakly affected the composition of gut microbiota and gene expression in the intestines.
  
  
  CONCLUSIONS
  The results suggest that increased oral commensals and gingival inflammation have limited roles in the pathological changes to adipose and liver tissues, which are important organs whose dysfunctions contribute to the development of periodontitis-related systemic diseases.
authors.affiliation: Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Laboratory for Intestinal Ecosystem, RCAI RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.affiliation: Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Arimatsu
authors.affiliation: Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Minagawa
authors.affiliation: Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.affiliation: Laboratory for Intestinal Ecosystem, RCAI RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamazaki
mesh_terms: D000103:Acetyl-CoA Carboxylase; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D016301:Alveolar Bone Loss / Q000382:microbiology / Q000473:pathology; D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification; D058491:Bacterial Load; D015415:Biomarkers; D004269:DNA, Bacterial / Q000302:isolation & purification; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000378:metabolism; D000069196:Gastrointestinal Microbiome / Q000235:genetics; D005786:Gene Expression Regulation; D005881:Gingiva / Q000737:chemistry / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D008026:Ligation / Q000009:adverse effects; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008437:Maxilla; D051379:Mice; D008810:Mice, Inbred C57BL; D008963:Molar; D009055:Mouth / Q000382:microbiology; D010518:Periodontitis / Q000378:metabolism* / Q000382:microbiology*; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D012336:RNA, Ribosomal, 16S / Q000235:genetics; D000685:Serum Amyloid A Protein / Q000032:analysis
chemical_list: D015415:Biomarkers; D004269:DNA, Bacterial; D015850:Interleukin-6; D012336:RNA, Ribosomal, 16S; D000685:Serum Amyloid A Protein; C577686:interleukin-6, mouse; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D000103:Acetyl-CoA Carboxylase; D005947:Glucose
keywords: inflammation; inflammatory mediator; periodontal medicine