EFFECTS OF EXERCISE AND GENETIC STRAIN ON BONE STRENGTH, MUSCULOSKELETAL GENE EXPRESSION AND ACTIVITY LEVELS IN C57BL/6J AND DBA/2J ADULT FEMALE MICE

Open Access
Author:
Preston, Holly
Graduate Program:
Kinesiology
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
August 13, 2009
Committee Members:
  • Neil Sharkey, Dissertation Advisor
  • Teresa Caroldean Lang, Committee Chair
  • Neil Sharkey, Committee Chair
  • Robert Barry Eckhardt, Committee Member
  • Douglas Cavener, Committee Member
Keywords:
  • exercise
  • bone
  • muscle
  • inbred mice
  • genetics
  • biomechanics
Abstract:
It is widely accepted that bones are able to adapt to changes in their loading environment by altering their structural strength. The details of this adaptation are still being explored, including elucidation of the genes involved. The main focus of this research was to further explore gene-environment interactions relative to bone adaptation. Increasing our understanding of these interactions may someday enable more individualized interventions that consider a person’s genotype when treating bone diseases such as osteoporosis. Adult female mice from two different inbred mouse strains with known differences in skeletal phenotypes, C57BL/6J (B6) and DBA/2J (D2), were exposed to two different regimens of mechanical loading: an aerobic based exercise intervention, treadmill running, and a more resistance based intervention, tower climbing. Ninety mice from both strains were equally divided into running, climbing and non-exercised groups. After five weeks of intervention, the mice were killed and the tissues were harvested from each mouse. Morphological parameters of the right femur from each mouse were measured and the bones were scanned using micro-computed tomography in order to evaluate the cross-sectional geometry of the mid-shaft. Mechanical properties of the femoral diaphysis were then assessed via three-point bending and the femoral neck was broken in a shear test. Differences were found as a function of treatment and genetic strain providing further evidence that bone adaptation in response to physiologically plausible interventions is dependent on genetic architecture. Total RNA from the gastrocnemius and from within the femoral diaphysis was extracted and gene expression was examined using Affymetrix microarrays for each strain and treatment group. Bone related genes were differentially expressed across the two mouse strains and some of these genes co-located with previously identified Quantitative Trait Loci (QTL) related to bone architecture and strength. Interestingly, a gene known to play a role in the regulation of the response of bone to mechanical loading had greater expression in tower climbers relative to the controls. Cage activity, body weight, and food consumption were repeatedly measured during the intervention and hindlimb muscle weights were measured during dissections of the mice. The results indicated differences in activity levels relative to genetic strain. Treadmill running was also shown to have an impact on normal home-cage activity. Treatment and genetic strain effects on body weight and food consumption were found as well. Muscle mass was affected by genetic strain, but treatment did not have an effect. These results provide valuable data for better interpretation of experimental manipulations exploring the influence of genetic strain and exercise on bone adaptation. Bone adaptation is a complex system that is strongly impacted by environmental demand and the genetics involved. Therefore, the gene-environment interaction is an important consideration when studying bone adaptation. There are also many indirect influences on bone such as muscle force that play a significant role. Understanding the response of bone to methods of enhanced mechanical loading via exercise and the role genes play is of significant value, as is gaining a greater understanding of known confounders.