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Friedman, M. A.

Publications and source records attributed to Friedman, M. A..

2 recordsLinked to original sources

Calcium- and Phosphorus-Supplemented Diet Increases Bone Volume After Four Weeks of High-Speed Treadmill Exercise in Adult Mice

Exercise has long-lasting benefits to bone health. Bone mass and the ability to exercise both decline with age, making it ideal to exercise earlier in life and to maximize gains in bone mass. Increasing strain on bone and frequency of loading during exercise can increase bone formation rate and cross-sectional area. Combining a short-term exercise program with a calcium- and phosphorus-supplemented diet increases cortical bone tissue mineral content (TMC) and area more than exercise alone in adult mice. It was hypothesized that combining high-speed running with a mineral-supplemented diet would lead to greater cortical TMC and area than high-speed running on a standard diet and low-speed running on a supplemented diet after 4 weeks. Male, 15-week old mice were assigned to 7 groups - a baseline group, non-exercised groups fed a control or supplemented diet, low-speed exercised groups fed a control or supplemented diet, and high-speed exercised groups fed a control or supplemented diet. Exercise consisted of 4 weeks of daily treadmill running for 20 min/day at 12 m/min or 20 m/min for low- and high-speed exercise, respectively. High-speed exercised mice had significantly lower body weight and lower tibial length after 4 weeks. Cortical TMC and area were significantly higher in high-speed exercised mice on the supplemented diet than high-speed exercised mice on the control diet. Trabecular bone volume (BV) and bone density were significantly higher in all groups on the supplemented diet than groups on the control diet, regardless of exercise. For mice on the control diet, non-exercised mice had significantly lower trabecular BV than baseline, while both speeds of exercise prevented this decline. There were few effects of exercise or diet on mechanical properties. For mice on the control diet, exercise significantly decreased serum PINP/CTX ratio on day 9 which may be preventing exercise from increasing bone mass or strength after only 4 weeks. For non-exercised mice on the supplemented diet, the serum PINP/CTX ratio on day 30 was significantly greater than for exercised mice, suggesting the supplemented diet may also lead to significantly greater bone mass in non-exercised mice if these interventions were extended beyond 4 weeks. Increasing treadmill speed can lower body weight while maintaining cortical and trabecular bone mass. A mineral-supplemented diet increases cortical and trabecular bone mass with high-speed exercise.

physiology

Genetic Variability affects the Skeletal Response to Unloading

Mechanical unloading decreases bone volume and strength. In humans and mice, bone mineral density is highly heritable, and in mice the response to changes in loading varies with genetic background. Thus, genetic variability may affect the response of bone to unloading. As a first step to identify genes involved in bone response to unloading, we evaluated the effects of unloading in eight inbred mouse strains: C57BL/6J, PWK/PhJ, WSB/EiJ, A/J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, and CAST/EiJ. C57BL/6J and NOD/ShiLtJ mice had the greatest unloading induced loss of diaphyseal cortical bone volume and strength. NZO/HlLtJ mice had the greatest metaphyseal trabecular bone loss, and C57BL/6J, WSB/EiJ, NOD/ShiLtJ, and CAST/EiJ mice had the greatest epiphyseal trabecular loss. Bone loss in the epiphyses displayed the highest heritability. With immobilization, mineral:matrix was reduced, and carbonate:phosphate and crystallinity were increased. A/J mice displayed the greatest unloading induced loss of mineral:matrix. Changes in gene expression in response to unloading were greatest in NOD/ShiLtJ and CAST/EiJ mice. The most upregulated genes in response to unloading were associated with increased collagen synthesis and extracellular matrix formation. Our results demonstrate a strong differential response to unloading as a function of strain. Diversity outbred (DO) mice are a high-resolution mapping population derived from these eight inbred founder strains. These results suggest DO mice will be highly suited for examining the genetic basis of the skeletal response to unloading.

genetics