Femoral morphology and cross-sectional geometry of adult myostatin-deficient mice

GDF-8, also known as myostatin, is a member of the transforming growth fact or-beta (TGF-beta) superfamily of secreted growth and differentiation facto rs that is expressed in vertebrate skeletal muscle. Myostatin functions as a negative regulator of skeletal muscle growth and myostatin null mice show a doubling of muscle mass compared with normal mice. We examined femoral m orphology of adult myostatin-deficient mice to assess the effects of muscle fiber hypertrophy and hyperplasia on bone shape and cross-sectional geomet ry, Femora of age- and weight-matched adult mice homozygous for the disrupt ed myostatin sequence were compared with those of wild-type controls (n = 8 per group), Results show that, as was the case in previous studies, myosta tin null mice have hindlimb muscle masses that are approximately double tho se of controls. Myostatin-deficient mice exhibit third trochanters that are significantly larger than those of controls, whereas the femoral midshafts of the control and experimental mice no not differ significantly from one another in cortical area, bending moment of inertia, and polar moment of in ertia. Our findings indicate that the increased muscle mass of myostatin-de ficient mice primarily affects sites of muscle insertion, but does not indu ce additional cortical bone deposition in the diaphysis relative to control s. We therefore conclude that the expanded third trochanters of myostatin-d eficient subjects result from tendon and Sharpey fiber expansion associated with muscle growth rather than cortical bone deposition in response to inc reased levels of mechanical stress. (C) 2000 by Elsevier Science Inc. All r ights reserved.