The effect of growth/differentiation factor-5 deficiency on femoral composition and mechanical behavior in mice.
A subclass of the bone morphogenetic proteins (BMPs), known as growth/differentiation factors (GDFs) 5, 6, and 7, have been shown to affect several skeletal processes, including endochondral ossification, synovial joint formation, and tendon and ligament repair. Mice deficient in GDF-5 have also been shown to exhibit biomechanical abnormalities in tendon that may be associated with altered type I collagen. The purpose of this study was to investigate the effect of GDF-5 deficiency on another type I collagen-rich tissue: cortical bone. Analyses were performed on femora from 8-week-old GDF-5-deficient male brachypodism mice. We hypothesized that GDF-5-deficient bones would exhibit altered geometric, structural, and material properties compared with control littermates. Mutant animals were significantly smaller in body mass than controls (-21%). Geometrically, mutant long bones were significantly shorter (-25%), had a lower polar moment of inertia (-34%), and a lower geometric strength indicator (analogous to the section modulus of a circular section) (-30%). When normalized by body mass, however, geometric differences were no longer significant. Structurally, GDF-5-deficient femora were weaker (-31%) and more compliant (-57%) than controls when tested to failure in torsion. Lower bone structural stiffness in the mutants was not completely explained by the smaller bone geometry, because mutant bones exhibited a significantly lower effective shear modulus (-36%). Although body mass did not fully explain the reduced structural strength in mutant bones, strength differences were adequately explained by bone cross-sectional geometry; maximum effective shear stress was not significantly different between mutants and controls, despite a statistically significant 6% lower ash fraction in mutant femora. No significant difference was detected in collagen content, as indicated by hydroxyproline per dry mass.
Mikic
Borjana
B
Picker Engineering Program, Smith College, Northampton, MA 01063, USA. bmikic@smith.edu
Battaglia
T C
TC
Taylor
E A
EA
Clark
R T
RT
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D024042:Collagen Type I / Q000032:analysis; D005269:Femur / Q000002:abnormalities* / Q000737:chemistry / Q000473:pathology*; D055428:Growth Differentiation Factor 5; D006720:Homozygote; D006909:Hydroxyproline / Q000032:analysis; D017880:Limb Deformities, Congenital / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D013314:Stress, Mechanical; D019415:Torque; D014102:Torsion Abnormality
D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D006909:Hydroxyproline