title: GDF-5 deficiency in mice leads to disruption of tail tendon form and function.
abstract: Although the biological factors which regulate tendon homeostasis are poorly understood, recent evidence suggests that Growth and Differentiation Factor-5 (GDF-5) may play a role in this important process. The purpose of this study was to investigate the effect of GDF-5 deficiency on mouse tail tendon using the brachypodism mouse model. We hypothesized that GDF-5 deficient tail tendon would exhibit altered composition, ultrastructure, and biomechanical behavior when compared to heterozygous control littermates. Mutant tail tendons did not display any compositional differences in sulfated glycosaminoglycans (GAG/DNA), collagen (hydroxyproline/DNA), or levels of fibromodulin, decorin, or lumican. However, GDF-5 deficiency did result in a 17% increase in the proportion of medium diameter (100-225 nm) collagen fibrils in tail tendon (at the expense of larger fibrils) when compared to controls (p < 0.05). Also, mutants exhibited a trend toward an increase in irregularly-shaped polymorphic fibrils (33% more, p > 0.05). While GDF-5 deficient tendon fascicles did not demonstrate any significant differences in quasistatic biomechanical properties, mutant fascicles relaxed 11% more slowly than control tendons during time-dependent stress-relaxation tests (p < 0.05). We hypothesize that this subtle alteration in time-dependent mechanical behavior is most-likely due to the increased prevalence of irregularly shaped type I collagen fibrils in the mutant tail tendons. These findings provide additional evidence to support the conclusion that GDF-5 may play a role in tendon homeostasis in mice.
authors.affiliation: Department of Orthopaedic Surgery, University of Virginia, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Clark
authors.forename: T L
authors.initials: TL
authors.lastname: Johnson
authors.forename: B J
authors.initials: BJ
authors.lastname: Schalet
authors.forename: L
authors.initials: L
authors.lastname: Davis
authors.forename: V
authors.initials: V
authors.lastname: Gaschen
authors.forename: E B
authors.initials: EB
authors.lastname: Hunziker
authors.forename: A
authors.initials: A
authors.lastname: Oldberg
authors.forename: B
authors.initials: B
authors.lastname: Mikic
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I / Q000096:biosynthesis* / Q000648:ultrastructure; D004247:DNA / Q000378:metabolism; D004548:Elasticity; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008970:Molecular Weight; D011509:Proteoglycans / Q000378:metabolism; D013314:Stress, Mechanical; D013623:Tail / Q000002:abnormalities* / Q000254:growth & development* / Q000648:ultrastructure; D013710:Tendons / Q000002:abnormalities* / Q000254:growth & development* / Q000648:ultrastructure
chemical_list: D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D011509:Proteoglycans; D004247:DNA