The Interplay of Exercise and Genetics in the Tibiae of Female C57BL/6J AND DBA/2J Mouse Strains

Open Access
- Author:
- Hernandez, Eleanore
- Graduate Program:
- Physiology
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- June 04, 2008
- Committee Members:
- Neil Sharkey, Thesis Advisor/Co-Advisor
- Keywords:
- exercise
inbred mouse strains
bone physiology - Abstract:
- Osteoporosis is a skeletal disease characterized by a progressive reduction in bone mineral density (BMD) that results in susceptibility to fractures and increased morbidity. Exercise is commonly advocated as a preventative strategy against the development of osteoporosis and as a treatment for individuals already affected. However, considerable variance in the utility of exercise or physical activity as an intervention has been observed, suggesting an intrinsic component. Defining interactions between environmental loading and genes will facilitate design of new interventions for the prevention and treatment of osteoporosis. The objective of this study was to examine the effects of exercise on skeletal strength and architecture in female C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains. Each strain was divided into the following exercise treatment groups: treadmill running, tower climbing, and non-exercised control. The treadmill regimen was performed 5 consecutive days per week for a total of 5 weeks with a gradual increase to a 25 degree incline at 15 m/min for 30 minutes/day. The tower climbing mice were continually housed in a cage equipped with a cylindrical tower 17 cm in diameter and 100 cm tall for a total of 5 weeks. For the first week, water bottles were adjusted from 20 to 100 cm from the bottom of the cage to train the animal to climb the tower. Upon completion of the five week exercise intervention, the tibiae were extracted and then analyzed using a Scanco Medical micro-computed tomography (µCT-40) instrument to obtain quantitative data of cortical and trabecular bone architecture. Following scanning, the tibial midshafts were tested to failure in three-point bending using a semi-hydraulic Materials Testing System (MTS) 858 MiniBionix apparatus. The proximal end was embedded and sectioned to qualitatively assess bone apposition using dynamic histomorphometry based upon fluorescent dyes that were administered during the 5 week exercise regimen. The distal segment of the tibia was dried and ashed to determine bone composition. Genetic strain and the type of exercise intervention significantly affected the outcome. Significant exercise treatment effects were identified for several measures including cortical thickness, trabecular bone volume fraction as well as trabecular number and thickness in B6 mice with the magnitude of effect dependent upon the intervention type, whereas no exercise treatment effect was observed in the D2 animals. Taken as a whole, these results demonstrate the impact of different types of exercise on skeletal architecture, strength, and composition as a function of genetic predisposition. A more complete understanding of the underlying factors of bone regulation may lead to improvements in recognizing individuals most at risk for developing osteoporosis as well as constructing effective patient-specific interventions.