Reactive oxygen species on bone mineral density and mechanics in Cu,Zn superoxide dismutase (Sod1) knockout mice.
Reactive oxygen species (ROS) play a role in a number of degenerative conditions including osteoporosis. Mice deficient in Cu,Zn-superoxide dismutase (Sod1) (Sod1(-/-) mice) have elevated oxidative stress and decreased muscle mass and strength compared to wild-type mice (WT) and appear to have an accelerated muscular aging phenotype. Thus, Sod1(-/-) mice may be a good model for evaluating the effects of free radical generation on diseases associated with aging. In this experiment, we tested the hypothesis that the structural integrity of bone as measured by bending stiffness (EI; N/mm(2)) and strength (MPa) is diminished in Sod1(-/-) compared to WT mice. Femurs were obtained from male and female WT and Sod1(-/-) mice at 8months of age and three-point bending tests were used to determine bending stiffness and strength. Bones were also analyzed for bone mineral density (BMD; mg/cc) using micro-computed tomography. Femurs were approximately equal in length across all groups, and there were no significant differences in BMD or EI with respect to gender in either genotype. Although male and female mice demonstrated similar properties within each genotype, Sod1(-/-) mice exhibited lower BMD and EI of femurs from both males and females compared with gender matched WT mice. Strength of femurs was also lower in Sod1(-/-) mice compared to WT as well as between genders. These data indicate that increased oxidative stress, due to the deficiency of Sod1 is associated with decreased bone stiffness and strength and Sod1(-/-) mice may represent an appropriate model for studying disease processes in aging bone.
Biomedical Engineering, University of Michigan, 2025 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Michael J
MJ
Smietana
Ellen M
EM
Arruda
John A
JA
Faulkner
Susan V
SV
Brooks
Lisa M
LM
Larkin
D000375:Aging / Q000473:pathology*; D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology*; D004548:Elasticity; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010024:Osteoporosis / Q000235:genetics / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014057:Tomography, X-Ray Computed
D017382:Reactive Oxygen Species; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1