Regulation of Bone mass in Myostatin Deficient Mice

DESCRIPTION (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.