GDF-5 deficiency in mice leads to disruption of tail tendon form and function.
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.
Clark
R T
RT
Department of Orthopaedic Surgery, University of Virginia, USA.
Johnson
T L
TL
Schalet
B J
BJ
Davis
L
L
Gaschen
V
V
Hunziker
E B
EB
Oldberg
A
A
Mikic
B
B
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
D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D011509:Proteoglycans; D004247:DNA