title: Hindlimb Skeletal Muscle Function and Skeletal Quality and Strength in +/G610C Mice With and Without Weight-Bearing Exercise.
abstract: Osteogenesis imperfecta (OI) is a heterogeneous heritable connective tissue disorder associated with reduced bone mineral density and skeletal fragility. Bone is inherently mechanosensitive, with bone strength being proportional to muscle mass and strength. Physically active healthy children accrue more bone than inactive children. Children with type I OI exhibit decreased exercise capacity and muscle strength compared with healthy peers. It is unknown whether this muscle weakness reflects decreased physical activity or a muscle pathology. In this study, we used heterozygous G610C OI model mice (+/G610C), which model both the genotype and phenotype of a large Amish OI kindred, to evaluate hindlimb muscle function and physical activity levels before evaluating the ability of +/G610C mice to undergo a treadmill exercise regimen. We found +/G610C mice hindlimb muscles do not exhibit compromised muscle function, and their activity levels were not reduced relative to wild-type mice. The +/G610C mice were also able to complete an 8-week treadmill regimen. Biomechanical integrity of control and exercised wild-type and +/G610C femora were analyzed by torsional loading to failure. The greatest skeletal gains in response to exercise were observed in stiffness and the shear modulus of elasticity with alterations in collagen content. Analysis of tibial cortical bone by Raman spectroscopy demonstrated similar crystallinity and mineral/matrix ratios regardless of sex, exercise, and genotype. Together, these findings demonstrate +/G610C OI mice have equivalent muscle function, activity levels, and ability to complete a weight-bearing exercise regimen as wild-type mice. The +/G610C mice exhibited increased femoral stiffness and decreased hydroxyproline with exercise, whereas other biomechanical parameters remain unaffected, suggesting a more rigorous exercise regimen or another exercise modality may be required to improve bone quality of OI mice.
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, USA.
authors.forename: Youngjae
authors.initials: Y
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Carleton
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA.
authors.forename: Bettina A
authors.initials: BA
authors.lastname: Gentry
authors.affiliation: Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, Kansas City, MO, USA.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Biomedical Sciences and Physical Therapy Program, University of Missouri, Columbia, MO, USA.
authors.forename: J Andries
authors.initials: JA
authors.lastname: Ferreira
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Salamango
authors.affiliation: Department of Orthopedics and Sports Medicine, University of Washington, Seattle, WA, USA.
authors.forename: MaryAnn
authors.initials: M
authors.lastname: Weis
authors.affiliation: Department of Biological Sciences, University of Missouri, Columbia, MO, USA.
authors.forename: Arin K
authors.initials: AK
authors.lastname: Oestreich
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, USA.
authors.forename: Ashlee M
authors.initials: AM
authors.lastname: Williams
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, USA.
authors.forename: Marcus G
authors.initials: MG
authors.lastname: McCray
authors.affiliation: Department of Orthopedics and Sports Medicine, University of Washington, Seattle, WA, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Eyre
authors.affiliation: Department of Biomedical Sciences and Physical Therapy Program, University of Missouri, Columbia, MO, USA.
authors.forename: Marybeth
authors.initials: M
authors.lastname: Brown
authors.affiliation: Department of Oral and Craniofacial Sciences, School of Dentistry, University of Missouri-Kansas City, Kansas City, MO, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, USA.|Department of Child Health, University of Missouri, Columbia, MO, USA.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Phillips
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D005269:Femur / Q000378:metabolism* / Q000473:pathology; D006614:Hindlimb / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010805:Physical Conditioning, Animal
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain
keywords: BONE; COLLAGEN CROSS-LINKS; EXERCISE; MUSCLE; OSTEOGENESIS IMPERFECTA
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