title: Characterization of oxidative stress status during diabetic bone healing.
abstract: Early events associated with bone healing in patients with type 2 diabetes mellitus appear to be delayed. Hyperglycaemia and an associated increase in oxidative stress are cited as potential factors leading to a change in cellular behaviour. Using an in vivo model monitoring bone formation around implants placed into rat mandibles, we have previously identified that the onset of cell proliferation and osteoblast differentiation are delayed and subsequently prolonged compared with normal bone. This study used the same implant model to characterize oxidative stress biomarkers and primary antioxidant enzyme profiles during diabetic bone healing in vivo. Implants were placed into the sockets of incisors extracted from the mandibles of normal Wistar and diabetic Goto-Kakizaki rats for 3 and 9 weeks after implant insertion. Histochemical analysis confirmed a delay in bone healing around implants in diabetic animals. Immunohistochemical localization of peri-cellular staining for protein carbonyl groups, as a biomarker of oxidized protein content, was slightly higher in diabetic granulation tissue compared with normal tissue. However, no differences were observed in the staining patterns of advanced glycation end products. Minimal differences were observed in the number of cells positive for cytoplasmic superoxide dismutase (SOD)1 or mitochondrial SOD2. Significantly, catalase was absent in diabetic tissues. The results suggest that the oxidative environment in healing bone is differentially affected by hyperglycaemia, particularly in relation to catalase. The significance of these observations for diabetic bone healing is discussed.
authors.affiliation: Tissue Engineering and Reparative Dentistry, School of Dentistry, Cardiff University, Heath Park, Cardiff, UK. waddingtonrj@cardiff.ac.uk
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Waddington
authors.forename: Amr
authors.initials: A
authors.lastname: Alraies
authors.forename: John S
authors.initials: JS
authors.lastname: Colombo
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: Sloan
authors.forename: Joji
authors.initials: J
authors.lastname: Okazaki
authors.forename: Ryan
authors.initials: R
authors.lastname: Moseley
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing