Observation Of Bone Metabolic Characters In Type 2 Diabetic Model Of Rats And Bone Expressions Of RAGE

Objective Advanced glycation end-products (AGEs) are chemical modifications of proteins by carbohydrates including those metabolic intermediates formed during the Maillard reaction,which contribute to be of significant pathophysiologic importance for the development of type 2 diabetes mellitus chronic complication. AGEs are common causative agents of diabetic osteoporosis and senile osteoporosis on the grounds that both diabetes mellitus and aging cause bone metabolic disorder, even osteoporosis. AGEs-RAGE interaction could especially contribute to development of bone metabolic disorder via disturbing bone remodeling. But less reserch reported about concentration of RAGE and Correlations with Bone Metabolic Related Indexes. To study the changes of bone concentrations of RAGE in type 2 diabetic model of rats, and investigate the correlations with the bone metabolic related indexes, combining with BMD in ex vivo,biomechanics and bone morphometry.Methods Sixty Wistar rats with three months old were randomly divided into 4 groups including male and female type 2 diabetes mellitus group and male and female normal control group. Type 2 diabetic models of male and female rats were set up by feeding high-glucose-high-fat diet and by injecting intraperitoneally with a low-dose streptozotocin(STZ). All rats were sacrificed 20 weeks after setting up model successfully. Serum AGEs were measured with fluorospectrophotometer. Bone concentrations of RAGE were mearured by immunohistochemistry. The ratio of ash weight to dry weight, bone mineral density(BMD)of femora and lumbar vertebra, the biomechanical indexes,bone morphometry parameters and the bone metabolic related indexes, such as serum Ca, P, bone gla protein(BGP), tartrate-resistant acid phosphatase(TRAP), insulin-like growth factor(IGF)-Ⅰwere also measured. Values are expressed as mean±SD. Statistical significance was evaluated by Independent–Samples T test for comparison. All statistical tests were performed on raw data by SPSS 13.0 process.Results Compared with normal control group, high glucose was induced in male and female rats of type 2 diabetes mellitus as the level of serum AGEs,FPG,FINS markedly increased(4.7±0.27 vs 2.41±0.28,9.38±0.86 vs 5.85±0.35,18.25±3.08 vs 12.20±1.80 in male;4.25±0.48 vs 2.20±0.37,8.63±0.81 vs 5.27±0.29,13.01±1.54 vs 9.12±0.96 in female). The ratio of ash weight to dry weight, BMD of femora and lumbar vertebra and the morphometry parameters icluding trabecular bone volume,trabecular thickness,trabecular number,bone mineralization rate,bone formation rate decreased rapidly by 8.45%,15.60%,21.33%,37.55%,14.74%,17.89%,24.49%,80.77% in male;6.14%,16.02%,14.07%,29.19%,19.17%,25.79%,31.91%,81.33% in female). No significant differences in serum concentrations of Ca and P were found. Serum concentrations of TRAP markedly increased(17.81±3.85 vs 8.59±3.35 in male;15.87±3.59 vs 8.64±2.83 in female), and BGP, IGF-Ⅰdecreased(5.79±1.69 vs 7.47±0.85,344.46±32.63 vs 435.58±33.29 in male;5.43±0.75 vs 7.14±0.70,361.90±46.17 vs 441.44±36.48 in female). There were even significant differences. Masccellule rate of RAGE increased strongly(1.14±0.35 vs 0.18±0.09 in male,0.75±0.17 vs 0.10±0.04 in female). RAGE showed a negative correlation with BMD,biomechanical parameters,trabecular thickness,trabecular bone volume,trabecular number,osteoblast surface,bone formation rate,BGP,IGF-Ⅰstrongly.Conclusions Bone concentrations of RAGE and serum concentrations of AGEs increased in this type 2 diabetic model rats, which consequently resulted in the descending bone mass and the changes of the bone biomechanical properties. AGEs-RAGE interaction could especially contribute to disturbed bone remodeling via osteoclasts and osteoblasts activation of nuclear factor-κB, which contribute to development of IGF-1,TNF-αand adhesion molecule. Achievement ratio and stability of diabetic model is related with sex of animals. Diabetic model of male rats is higher in achievement ratio and shorter in time consuming than that of female rats.