Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0205700 (ash)
 15,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The effect of growth/differentiation factor-5 deficiency on femoral composition and mechanical behavior in mice. 1199 12

The growth/differentiation factors (GDFs) are a subfamily of bone morphogenetic proteins (BMPs) known to play a role in a variety of skeletal processes. Previous work using the brachypod mouse demonstrated that mice deficient in GDF-5 have long bones with diminished material properties and ash content compared with control littermates. Our aim was to examine the role of a related GDF family member, GDF-7 (BMP-12), in cortical bone by examining the geometric and material contributions to whole bone structural behavior in GDF-7-deficient mice. Femora from 16-week-old GDF-7 -/- animals had significantly smaller bone cross-sectional geometric parameters (e.g., -20% medial/lateral and anterior/posterior moments of inertia). Despite having smaller bone cross-sections, all structural parameters obtained from four-point bending tests were comparable to those of wild-type bones due to elevated cortical bone material properties (+18% modulus of elasticity, +28% yield strength, and +18% ultimate strength). No significant differences in ash content or collagen content were detected, however. These data suggest that GDF-7 deficiency is associated with elevated cortical bone material properties that compensate for decreased geometric properties, thereby preserving bone structural integrity. The compositional and/or microstructural bases for these altered material properties remain to be determined, however.
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PMID:Geometric and material contributions to whole bone structural behavior in GDF-7-deficient mice. 1675 9