Muscle-bone interactions in dystrophin-deficient and myostatin-deficient mice

Eric Montgomery, Catherine Pennington, Carlos M. Isales, Mark W. Hamrick

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

We have investigated muscle-bone interactions using two mouse mutants that are known to differ from normal mice in skeletal muscle growth and development: mice lacking myostatin (GDF8) and mice lacking dystrophin (mdx). Myostatin-deficient mice show increased muscle size and strength compared to normal mice, whereas the mdx mouse is a well-established animal model for Duchenne muscular dystrophy. The mdx mice have significantly larger hindlimb muscles than controls, and histological sections of the quadriceps muscles show dystrophic changes with extensive fibrosis. Femoral bone mineral density (BMD) and fracture strength (Fu) are significantly greater in mdx mice than controls, and these variables are more strongly correlated with quadriceps muscle mass than with body mass. In contrast, mdx mice do not shower high bone mineral density in the spine relative to controls, whereas myostatin-deficient mice have significantly increased BMD in the lumbar spine compared to normal mice. Both mdx mice and myostatin-deficient mice have expanded femoral trochanters for attachment of large hindlimb muscles, and both mutant strains show increased cross-sectional area moments of inertia mediolaterally (Iyy) but not anteroposteriorly (Ixx) compared to normal mice. These data suggest that lean (muscle) mass is a significant determinant of bone mineral density and strength in the limb skeleton, even when accompanied by a dystrophic phenotype. Likewise, increased muscle mass produces a marked increase in the external dimensions of muscle attachment sites, even when increased muscle size is accompanied by extensive fibrosis and muscle weakness.

Original languageEnglish (US)
Pages (from-to)814-822
Number of pages9
JournalAnatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology
Volume286
Issue number1
DOIs
StatePublished - Sep 1 2005

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Keywords

  • Bone mass
  • Bone mineral density
  • Muscle strength
  • Spine

ASJC Scopus subject areas

  • Anatomy
  • Agricultural and Biological Sciences (miscellaneous)

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