(Verbatim from the Applicant): The primary objective of the proposed Academic Research Enhancement Award is to investigate the influence of muscle strength on bone mass using a new mouse model. Specifically, this study evaluates multiple working hypotheses concerning the effects of increased muscle mass on activity level, bone cross-sectional geometry, bone mass, mineral content, and microstructure. These hypotheses are tested by comparing locomotor activity, growth hormone levels, and bone structure between mice deficient in growth and differentiation factor-8 (myostatin) and wild-type controls. Myostatin functions as a negative regulator of skeletal muscle growth and myostatin null mice show a doubling of muscle fiber size and number compared to normal mice. The primary factor leading to the onset of osteoporosis is bone loss. One preventative and therapeutic approach for minimizing the potentially disastrous affects of bone loss during life is to increase peak bone mass by increasing muscle strength. The proposed study, by critically evaluating the effects of increased muscle mass on bone strength during postnatal growth, will expand significantly upon our current understanding of the mechanisms important for generating and maintaining healthy bone structure in adults. This enhancement award will also engage undergraduate students from two programs at Kent State University, the McNair Scholars and Ohio Board of Regents STARS programs, in mentored bone biology research. The proposed project will therefore provide new training opportunities for students from populations traditionally underrepresented in the biomedical research community.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15AR047655-01
Application #
6314913
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Program Officer
Sharrock, William J
Project Start
2001-04-11
Project End
2003-03-31
Budget Start
2001-04-11
Budget End
2003-03-31
Support Year
1
Fiscal Year
2001
Total Cost
$142,000
Indirect Cost
Name
Kent State University at Kent
Department
Social Sciences
Type
Schools of Arts and Sciences
DUNS #
041071101
City
Kent
State
OH
Country
United States
Zip Code
44242
Hamrick, M W; Skedros, J G; Pennington, C et al. (2006) Increased osteogenic response to exercise in metaphyseal versus diaphyseal cortical bone. J Musculoskelet Neuronal Interact 6:258-63
Hamrick, Mark W; Pennington, Catherine; Byron, Craig D (2003) Bone architecture and disc degeneration in the lumbar spine of mice lacking GDF-8 (myostatin). J Orthop Res 21:1025-32
Hamrick, Mark W (2003) Increased bone mineral density in the femora of GDF8 knockout mice. Anat Rec A Discov Mol Cell Evol Biol 272:388-91
Hamrick, M W; McPherron, A C; Lovejoy, C O (2002) Bone mineral content and density in the humerus of adult myostatin-deficient mice. Calcif Tissue Int 71:63-8