title: Patterns of diabetic periodontal wound repair: a study using micro-computed tomography and immunohistochemistry.
abstract: BACKGROUND
  Diabetes is known to impair wound healing and deteriorate the periodontal condition. There is limited information about the patterns and events associated with periodontal wound repair. In this study, we evaluate the dynamics of periodontal wound repair using micro-computed tomography (microCT) and immunohistochemistry.
  
  
  METHODS
  Thirty-six male rats were used, and diabetes was induced by streptozotocin. The maxillary first molars were extracted, and a tooth-associated osseous defect was created in the extraction area. Animals were sacrificed after 7, 14, and 21 days. Volumetry and distribution of bone trabeculae were evaluated by microCT imaging. The patterns of healing and collagen alignment were evaluated by histology. Advanced glycation end-product (AGE) deposition and expression of the receptor for AGEs (RAGE), tartrate-resistant acid phosphatase, and proliferating cell nuclear antigen were evaluated by histochemical and immunohistochemical staining.
  
  
  RESULTS
  Diabetic animals demonstrated a significantly reduced bone volume and trabecular number as well as thinner trabeculae and more trabecular separation in osseous defects. The early stage was characterized by significantly reduced cellular proliferation and prolonged active inflammation without evident bone resorption, whereas delayed recovery of collagen realignment, matrix deposition, and bone turnover was noted in later stages. Although AGEs and RAGE were present during healing in diabetes and controls, a stronger and more persistent level of expression was observed in the group with diabetes
  
  
  CONCLUSIONS
  Diabetes significantly delayed osseous defect healing by augmenting inflammation, impairing proliferation, and delaying bone resorption. The AGE-RAGE axis can be activated under metabolic disturbance and inflammation.
authors.affiliation: Faculty of Dentistry, National University of Singapore, Singapore, Singapore. dencpc@nus.edu.sg
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Chang
authors.forename: Min-Chun
authors.initials: MC
authors.lastname: Chung
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Chien
authors.forename: Jason C
authors.initials: JC
authors.lastname: Lim
authors.forename: Kaicheng
authors.initials: K
authors.lastname: Liang
authors.forename: Li Yen
authors.initials: LY
authors.lastname: Chong
authors.forename: Yen-Ping
authors.initials: YP
authors.lastname: Kuo
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.forename: Huan-Ching
authors.initials: HC
authors.lastname: Chiang
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D016301:Alveolar Bone Loss / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D000818:Animals; D016723:Bone Remodeling; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology*; D024022:Fibrillar Collagens / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000032:analysis; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010518:Periodontitis / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis; D000071681:Tartrate-Resistant Acid Phosphatase; D014945:Wound Healing / Q000502:physiology*; D055114:X-Ray Microtomography
chemical_list: D024022:Fibrillar Collagens; D017127:Glycation End Products, Advanced; D007527:Isoenzymes; D018809:Proliferating Cell Nuclear Antigen; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase