title: Adverse Effects of Diabetes Mellitus on the Skeleton of Aging Mice.
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.
authors.affiliation: Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, UAM, and Red Temática Cooperativa de Envejecimiento y Fragilidad (RETICEF), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Portal-Núñez
authors.affiliation: Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, UAM, and Red Temática Cooperativa de Envejecimiento y Fragilidad (RETICEF), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Ardura
authors.affiliation: Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, UAM, and Red Temática Cooperativa de Envejecimiento y Fragilidad (RETICEF), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Departamento de Química Inorgánica y Bioinorgánica, Facultad de Farmacia, Universidad Complutense (UCM), Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lozano
authors.affiliation: Departamento de Fisiología (Fisiología Animal II), Facultad de Ciencias Biológicas, UCM, and RETICEF, ISCIII, Madrid, Spain.
authors.forename: Oskarina Hernández
authors.initials: OH
authors.lastname: Bolívar
authors.affiliation: Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, UAM, and Red Temática Cooperativa de Envejecimiento y Fragilidad (RETICEF), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: López-Herradón
authors.affiliation: Centro de Investigaciones Biomédicas en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Gutiérrez-Rojas
authors.affiliation: ActiveLife Scientific, Santa Bárbara, California.
authors.forename: Alexander
authors.initials: A
authors.lastname: Proctor
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Bram
authors.initials: B
authors.lastname: van der Eerden
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: Schreuders-Koedam
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: van Leeuwen
authors.affiliation: Department of Pharmacology and IDM, Universidad de Valencia, Burjasot, Valencia, and RETICEF, ISCIII, Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Alcaraz
authors.affiliation: Molecular Imaging Unit, National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Mulero
authors.affiliation: Departamento de Fisiología (Fisiología Animal II), Facultad de Ciencias Biológicas, UCM, and RETICEF, ISCIII, Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: de la Fuente
authors.affiliation: Laboratorio de Metabolismo Mineral y Óseo, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, UAM, and Red Temática Cooperativa de Envejecimiento y Fragilidad (RETICEF), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Esbrit
mesh_terms: D000375:Aging; D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D010012:Osteogenesis / Q000502:physiology*; D010024:Osteoporosis / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
keywords: Aging; Diabetes mellitus; Mice; Osteoporosis