1. Adverse Effects of Diabetes Mellitus on the Skeleton of Aging Mice.
- Author
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Portal-Núñez, Sergio, Antonio Ardura, Juan, Lozano, Daniel, Hernández Bolívar, Oskarina, López-Herradón, Ana, Gutiérrez-Rojas, Irene, Proctor, Alexander, van der Eerden, Bram, Schreuders-Koedam, Marijke, van Leeuwen, Johannes, José Alcaraz, María, Mulero, Francisca, de la Fuente, Mónica, Esbrit, Pedro, Ardura, Juan Antonio, Bolívar, Oskarina Hernández, and Alcaraz, María José
- Subjects
DIABETES ,AGE factors in disease ,STREPTOZOTOCIN ,VASCULAR endothelial growth factor receptors ,PEROXISOME proliferator-activated receptors ,LABORATORY mice ,DIABETES complications ,OSTEOPOROSIS diagnosis ,BONE remodeling ,AGING ,ANIMAL experimentation ,BONE growth ,COMPUTED tomography ,LUMBAR vertebrae ,MICE ,OSTEOPOROSIS ,BONE density - Abstract
In the present study, the possibility that a diabetic (DM) status might worsen age-related bone deterioration was explored in mice. Male CD-1 mice aged 2 (young control group) or 16 months, nondiabetic or made diabetic by streptozotocin injections, were used. DM induced a decrease in bone volume, trabecular number, and eroded surface, and in mineral apposition and bone formation rates, but an increased trabecular separation, in L1-L3 vertebrae of aged mice. Three-point bending and reference point indentation tests showed slight changes pointing to increased frailty and brittleness in the mouse tibia of diabetic old mice. DM was related to a decreased expression of both vascular endothelial growth factor and its receptor 2, which paralleled that of femoral vasculature, and increased expression of the pro-adipogenic gene peroxisome proliferator-activated receptor γ and adipocyte number, without affecting β-catenin pathway in old mouse bone. Concomitant DM in old mice failed to affect total glutathione levels or activity of main anti-oxidative stress enzymes, although xanthine oxidase was slightly increased, in the bone marrow, but increased the senescence marker caveolin-1 gene. In conclusion, DM worsens bone alterations of aged mice, related to decreased bone turnover and bone vasculature and increased senescence, independently of the anti-oxidative stress machinery. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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