Femoral histomorphometric analysis of C57Bl6 mice treated with anti-activin A and anti-myostatin monoclonal antibodies
Lawrence Mason1, Catherine Omosule2, Charlotte Phillips2
1Department of Biology, Belhaven University, Jackson, MS
2Department of Biochemistry, The University of Missouri, Columbia, MO
Osteoporosis is a disease of reduced bone quality and quantitative loss in bone mineral density (BMD) that results in skeletal fractures. Peak bone mass is a critical determinant of one’s bone health and hence the risk of osteoporosis in later life, and is influenced by genetic and environmental factors. In this study, we investigated the possibility of improving peak bone mass in male C57Bl6 mice via pharmacological inhibition of activin A and myostatin.
Activin A and myostatin are known regulators of muscle mass in primates as well as mice. Previous studies have demonstrated that the combined inhibition of myostatin and activin A in mice results in increased muscle mass. Additionally, in mouse models of musculoskeletal disorders such as osteogenesis imperfecta (OI) and duchenne muscular dystrophy, inhibition of activin A and myostatin resulted in improved bone strength due to the mechanotransductive response of bone to increased muscle load. In this study, the individual effects of anti-myostatin and anti-activin A antibody treatment will be delineated. In this experiment, male C57Bl6 mice were treated with 10mg/Kg of body weight of either therapeutic agent (anti-activin A or anti-myostatin antibodies) or a control antibody twice per week beginning at 5 weeks of age. At 16 weeks of age, mice were sacrificed, and their bones harvested. To determine the effects of anti-activin A and anti-myostatin treatment on wild-type mice, femoral histomorphometry was performed to quantify mineralized bone area, osteoclast and osteoblast cell numbers, and cell surface area of mineralized bone. In future studies, we will examine femoral histomorphometry of OI mice treated with these specific agents to determine their therapeutic potential of enhancing OI bone formation and quality. Successful increases in peak muscle and bone mass with treatment has potential application of the treatments to future human trials.