title: Altered gene expression in gingival tissues and enhanced bone loss in rats with diabetes with experimental periodontitis.
abstract: BACKGROUND
  Systemic hyperglycemia is clearly related to severity of periodontitis, meaning that periodontitis can be exacerbated by diabetes mellitus (DM). However, the biologic mechanisms responsible for this relationship remain unclear. Thus, in this study, the global gene expression in gingival tissue with periodontitis is profiled in Zucker diabetic fatty (ZDF) rats compared with Zucker normoglycemic littermates (Lean).
  
  
  METHODS
  At age 8 weeks, ZDF and Lean rats received ligature placement around the maxillary right second molar. At 0, 14, 28, 42, and 56 days after ligature placement, the maxilla around the molar was analyzed using microcomputed tomography. Two and 7 days after ligature placement, total RNA in the gingival tissue was isolated, and gene expression analysis was conducted using a rat oligo array. To validate the microarray findings, the selected genes were analyzed using real-time quantitative polymerase chain reaction assays.
  
  
  RESULTS
  There was a significant difference regarding the average amount of bone resorption between ZDF and Lean rats from days 14 to 56. On day 2, it was found that 113 genes were regulated (20 upregulated, 93 downregulated) in the presence of DM. Lipopolysaccharide binding protein (LBP) messenger RNA (mRNA) expression was significantly higher in gingival tissue with periodontitis from ZDF rats compared with that from Lean rats. On day 7, interleukin (IL)-10 and IL-24 mRNA levels were significantly lower, whereas IL-2 level was significantly elevated.
  
  
  CONCLUSIONS
  The results of this study indicate that the role of DM in modulating bone breakdown related to periodontitis may involve an increased level of LBP and reduced levels of T-helper 2 cytokines.
authors.affiliation: Department of Periodontology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Soboku
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Fujita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeda
authors.forename: Keiko
authors.initials: K
authors.lastname: Naruse
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Matsubara
authors.forename: Toshihide
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D016301:Alveolar Bone Loss / Q000209:etiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005881:Gingiva / Q000378:metabolism*; D021621:Imaging, Three-Dimensional / Q000379:methods; D007328:Insulin / Q000097:blood; D016753:Interleukin-10 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D008070:Lipopolysaccharides / Q000032:analysis; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010518:Periodontitis / Q000209:etiology*; D012313:RNA / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D055114:X-Ray Microtomography / Q000379:methods; D000099231:Lipopolysaccharide-Binding Protein; D000099180:Interleukin-24
chemical_list: D000209:Acute-Phase Proteins; D001786:Blood Glucose; D002352:Carrier Proteins; D016207:Cytokines; D007328:Insulin; D016753:Interleukin-10; D007376:Interleukin-2; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012313:RNA; D014280:Triglycerides; D000099231:Lipopolysaccharide-Binding Protein; C413022:IL24 protein, rat; D000099180:Interleukin-24