title: Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.
abstract: Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates.
  
  
  BACKGROUND
  Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass.
  
  
  METHODS
  To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity.
  
  
  RESULTS
  +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling.
  
  
  CONCLUSIONS
  Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.
authors.affiliation: Department of Biological Sciences, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Oestreich
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Carleton
authors.affiliation: Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
authors.forename: X
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Gentry
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Raw
authors.affiliation: Department of Biomedical Sciences and Physical Therapy Program, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.affiliation: Department of Orthopaedic Surgery and Bioengineering, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Pfeiffer
authors.affiliation: Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA. phillipscl@missouri.edu.|Department of Child Health, University of Missouri, 117 Schweitzer Hall, Columbia, MO, 65211, USA. phillipscl@missouri.edu.
authors.forename: C L
authors.identifier: http://orcid.org/0000-0002-7761-3783
authors.initials: CL
authors.lastname: Phillips
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001696:Biomechanical Phenomena; D001835:Body Weight / Q000502:physiology; D015519:Bone Density / Q000502:physiology; D016723:Bone Remodeling / Q000502:physiology; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology*; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000473:pathology*; D009154:Mutation; D055435:Myostatin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D009929:Organ Size / Q000502:physiology; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D010641:Phenotype; D013977:Tibia / Q000473:pathology; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D015415:Biomarkers; C525912:Mstn protein, mouse; D055435:Myostatin; D003094:Collagen
keywords: Biomechanics; Bone; Myostatin; Osteogenesis imperfecta; Raman spectroscopy; Skeletal muscle