GDF-5 deficiency in mice leads to disruption of tail tendon form and function

Although the biological factors which regulate tendon homeostasis are poorl y understood, recent evidence suggests that Growth and Differentiation Fact or-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 tend on using the brachypodism mouse model. We hypothesized that GDF-5 deficient tail tendon would exhibit altered composition, ultrastructure, and biomech anical behavior when compared to heterozygous control littermates. Mutant t ail tendons did not display any compositional differences in sulfated glyco saminoglycans (GAG/DNA), collagen (hydroxyproline/DNA), or levels of fibrom odulin, 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 control s (p < 0.05). Also, mutants exhibited a trend toward an increase in irregul arly-shaped polymorphic fibrils (33% more, p > 0.05). While GDF-5 deficient tendon fascicles did not demonstrate any significant differences in quasis tatic biomechanical properties, mutant fascicles relaxed 11% more slowly th an control tendons during time-dependent stress-relaxation tests (p < 0.05) . We hypothesize that this subtle alteration in time-dependent mechanical b ehavior is most-likely due to the increased prevalence of irregularly shape d type I collagen fibrils in the mutant tail tendons. These findings provid e additional evidence to support the conclusion that GDF-5 may play a role in tendon homeostasis in mice.