title: Aminoguanidine inhibits the AGE-RAGE axis to modulate the induction of periodontitis but has limited effects on the progression and recovery of experimental periodontitis: a preliminary study.
abstract: BACKGROUND
  Advanced glycation end products (AGE) have been found in inflamed gingival tissue and have been shown to interfere with the integrity of extracellular matrix and cell-matrix interactions. This study aims to investigate the modulatory effect of aminoguanidine (AG), an AGE inhibitor, in various stages of experimental periodontitis.
  
  
  METHODS
  Thirty-six Sprague-Dawley rats were used. AG or normal saline (NS) was systemically administered in the induction, progression, and recovery phases of ligature-induced periodontitis. Dynamic changes of the periodontium were evaluated by microcomputed tomography, histology, and immunohistochemistry of the receptor for AGE (RAGE). Molecular mechanisms were evaluated by myeloperoxidase activity, gene expression of RAGE, and markers associated with tissue repair and homeostasis, including vascular endothelial growth factor (VEGF), type I collagen, fibronectin, and periostin.
  
  
  RESULTS
  AG appeared to inhibit the degradation of the collagen matrix in the induction phase but promoted collagen reorganization in the progression and recovery phases of experimental periodontitis. In the induction sites, periodontal bone loss was significantly reduced (P <0.05), with significantly reduced RAGE (P <0.05) and significantly elevated fibronectin and periostin levels (P <0.01). No significant alterations in the levels of myeloperoxidase, VEGF, and collagen were noted. In the progression and recovery sites, similar trends were observed, with insignificant differences relative to NS-treated animals.
  
  
  CONCLUSIONS
  AG reduced periodontal bone loss during the induction of experimental periodontitis, and the effects appeared to be insignificant in the progression and recovery phases. This modulation was related to the inhibition of the AGE-RAGE axis to resume cell-matrix interactions and maintain tissue integrity.
authors.affiliation: Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Chang
authors.forename: Li Yen
authors.initials: LY
authors.lastname: Chong
authors.forename: Sheng-Chueh
authors.initials: SC
authors.lastname: Tsai
authors.forename: Lum Peng
authors.initials: LP
authors.lastname: Lim
mesh_terms: D016301:Alveolar Bone Loss / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D000539:Alveolar Process / Q000187:drug effects / Q000473:pathology; D043925:Angiogenesis Inducing Agents / Q000032:analysis; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000187:drug effects; D024042:Collagen Type I / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D005353:Fibronectins / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000187:drug effects*; D006146:Guanidines / Q000627:therapeutic use*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010518:Periodontitis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D010519:Periodontium / Q000187:drug effects / Q000473:pathology; D009195:Peroxidase / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D005353:Fibronectins; D017127:Glycation End Products, Advanced; D006146:Guanidines; C512836:Postn protein, rat; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D009195:Peroxidase; D019001:Nitric Oxide Synthase; C004479:pimagedine