GDF-5 deficiency in mice alters the ultrastructure, mechanical properties and composition of the Achilles tendon

• Published in: Journal of orthopaedic research 2001-05, Vol.19 (3), p.365-371
• Main Authors: Mikic, Borjana, Schalet, Benjamin J., Clark, Randall T., Gaschen, Veronique, Hunziker, Ernst B.
• Format: Article
• Language: English
• Subjects: Achilles Tendon - chemistry; Achilles Tendon - physiology; Achilles Tendon - ultrastructure; Animals; Bone Morphogenetic Proteins; Collagen - ultrastructure; DNA - analysis; Glycosaminoglycans - analysis; Growth Differentiation Factor 5; Growth Substances - deficiency; Growth Substances - genetics; Heterozygote; Hydroxyproline - analysis; Male; Mice; Mice, Knockout - genetics; Microscopy, Electron; Stress, Mechanical
• ISSN: 0736-0266; 1554-527X
• DOI: 10.1016/S0736-0266(00)90018-4

Acromesomelic dysplasia of the Hunter–Thompson and Grebe types are rare human disorders based on growth/differentiation factor (GDF)-5/CDMP-1 genetic mutations. Numerous skeletal abnormalities are present in these individuals, including shortened limb bones and severe dislocations of the knee. In the GDF-5 deficient brachypodism mouse, similar, although less severe, phenotypes are observed. It is unknown whether the joint dislocations observed in these disorders are due to a defect in the original formation of joints such as the knee, or to abnormalities in the tendons and ligaments themselves. We hypothesized that tendons from GDF-5 deficient mice would exhibit altered composition, mechanical properties, and ultrastructure when compared with heterozygous control littermates. GDF-5 deficient Achilles tendons were structurally weaker than controls, and structural strength differences appeared to be caused by compromised material properties: after normalizing by collagen per unit length, mutant tendons were still 50% weaker ( P