The effect of growth/differentiation factor-5 deficiency on femoral composition and mechanical behavior in mice

Bone. 2002 May;30(5):733-7. doi: 10.1016/s8756-3282(02)00699-3.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / genetics*
  • Collagen Type I / analysis
  • Femur / abnormalities*
  • Femur / chemistry
  • Femur / pathology*
  • Growth Differentiation Factor 5
  • Homozygote
  • Hydroxyproline / analysis
  • Limb Deformities, Congenital / genetics*
  • Limb Deformities, Congenital / pathology*
  • Male
  • Mice
  • Mice, Mutant Strains
  • Stress, Mechanical
  • Torque
  • Torsion Abnormality


  • Bone Morphogenetic Proteins
  • Collagen Type I
  • Gdf5 protein, mouse
  • Growth Differentiation Factor 5
  • Hydroxyproline