title: Glycated matrix up-regulates inflammatory signaling similarly to Porphyromonas gingivalis lipopolysaccharide.
abstract: OBJECTIVE
  Hyperglycemia and advanced glycation end-products (AGEs) have been hypothesized as the etiologic factors of diabetic periodontitis. The aim of this study was to clarify in greater detail the patterns of AGE-mediated periodontal inflammation under various physiological conditions.
  
  
  METHODS
  The deposition of AGEs and expression of the receptor for AGEs (RAGE) were identified by immunohistochemistry in Sprague-Dawley rats with experimentally induced periodontitis or diabetes. Human periodontal ligament cells (PDLCs) and mesenchymal stem cells (MSCs) were cultured under simulated conditions of hyperglycemia, Porphyromonas gingivalis lipopolysaccharide (LPS) stimulation and matrix glycation. Cell viability and expression of toll-like receptors (TLRs), Rage, an inflammatory signaling initiator (nuclear factor kappa light chain enhancer of activator β cells), an oxidative stressor (heme oxygenase-1) and collagen synthesis (type I and type IV) genes were evaluated.
  
  
  RESULTS
  The deposition of AGEs and the expression of Rage were evident in the inflamed periodontal tissues in all rats and appeared to be enhanced in rats with diabetes. Matrix glycation augmented cytotoxicity, up-regulated RAGE and TLRs in both PDLCs and MSCs, and significantly activated downstream inflammatory signaling in MSCs. Oxidative stress was significantly increased under matrix glycation in both PDLCs and MSCs and was significantly increased at a high-glucose concentration in MSCs. A consistent decrease in expression of type I and type IV collagens was observed in MSCs, but a delayed reduction was noted in PDLCs.
  
  
  CONCLUSIONS
  Matrix glycation modulated cell behavior to induce inflammation equivalent to that produced by incubation with P. gingivalis LPS. Periodontal inflammation also led to matrix glycation, thus demonstrating a definite interaction between diabetes and periodontitis.
authors.affiliation: Faculty of Dentistry, National University of Singapore, Singapore, Singapore. dencpc@nus.edu.sg
authors.forename: P-C
authors.initials: PC
authors.lastname: Chang
authors.forename: L-Y
authors.initials: LY
authors.lastname: Chien
authors.forename: L Y
authors.initials: LY
authors.lastname: Chong
authors.forename: Y-P
authors.initials: YP
authors.lastname: Kuo
authors.forename: J-K
authors.initials: JK
authors.lastname: Hsiao
mesh_terms: D016301:Alveolar Bone Loss / Q000276:immunology / Q000473:pathology; D000818:Animals; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000032:analysis; D024043:Collagen Type II / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000276:immunology; D017127:Glycation End Products, Advanced / Q000276:immunology*; D051547:Heme Oxygenase-1 / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology; D052002:NF-kappa B p50 Subunit / Q000032:analysis; D018384:Oxidative Stress / Q000502:physiology; D010513:Periodontal Ligament / Q000166:cytology / Q000276:immunology*; D010518:Periodontitis / Q000276:immunology / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013311:Streptozocin; D051193:Toll-Like Receptors / Q000032:analysis; D015854:Up-Regulation / Q000276:immunology
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D017127:Glycation End Products, Advanced; D008070:Lipopolysaccharides; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; D013311:Streptozocin; D051547:Heme Oxygenase-1