title: Osseous wound repair under inhibition of the axis of advanced glycation end-products and the advanced glycation end-products receptor.
abstract: OBJECTIVE
  Blockade of advanced glycation end-products (AGE) is able to reduce diabetic complications and control periodontitis. This study aimed to determine whether the application of aminoguanidine (AG), an AGE inhibitor, or N-phenacylthiazolium bromide (PTB), an AGE breaker, facilitates the healing of an osseous wound in non-diabetic animals.
  
  
  METHODS
  2.6 mm diameter full-thickness osseous wounds were created bilaterally in 54 healthy Sprague-Dawley rats. Rats received daily normal saline, AG, or PTB injections respectively and were euthanized after 7 days, 14 days, or 28 days (n = 6). The wound healing pattern was assessed by micro-computed tomography, histology, histochemistry for the fiber arrangement, and the gene expression levels of AGE receptor, tumor necrosis factor-α, type I collagen, and fibronectin.
  
  
  RESULTS
  Under the AG and PTB administration, osteogenesis was apparently promoted in the early stages of healing, but the union of the osseous wound and the fibril re-arrangement was apparently retarded. No significant difference was found in any of the micro-computed tomography parameters as compared to the control in the first 14 days, whereas the relative bone volume was significantly higher in the control at Day 28. AGE receptor and tumor necrosis factor-α were depressed in the PTB group, but only temporarily at Day 14 in the AG group. Therefore, at Day 14, type I collagen was significantly upregulated in the PTB group, and fibronectin was significantly increased in the AG group.
  
  
  CONCLUSIONS
  Anti-AGE agents reduced inflammation but did not apparently facilitate osteogenesis during the osseous wound repair.
authors.affiliation: Institute of Molecular and Cellular Biology, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Sheng-Chueh
authors.initials: SC
authors.lastname: Tsai
authors.affiliation: Department of Periodontology, Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Jheng
authors.affiliation: Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chen-Ying
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Periodontology, Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Taiwan Mouse Clinics-National Phenotyping and Drug Testing Center, National Research Program for Biopharmaceuticals, National Science Council, Taipei, Taiwan.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Lin
authors.affiliation: Taiwan Mouse Clinics-National Phenotyping and Drug Testing Center, National Research Program for Biopharmaceuticals, National Science Council, Taipei, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Periodontology, Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: changpc@ntu.edu.tw.
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Chang
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006146:Guanidines / Q000008:administration & dosage*; D008297:Male; D008338:Mandibular Injuries / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D013844:Thiazoles / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: C000593874:Ager protein, rat; D024042:Collagen Type I; D005353:Fibronectins; D017127:Glycation End Products, Advanced; D006146:Guanidines; C101705:N-phenacylthiazolium bromide; D000067759:Receptor for Advanced Glycation End Products; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C004479:pimagedine
keywords: N-phenacylthiazolium bromide; advanced glycation end-product; aminoguanidine; gene expression; micro-computed tomography