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

Acromesomelic dysplasia of the Hunter-Thompson and Grebe types are rare hum an 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 th e GDF-5 deficient brachypodism mouse, similar, although less severe, phenot ypes are observed. It is unknown whether the joint dislocations observed in these disorders are due to a defect in the original formation of joints su ch as the knee, or to abnormalities in the tendons and ligaments themselves . We hypothesized that tendons from GDF-5 deficient mice would exhibit alte red composition, mechanical properties. and ultrastructure when compared wi th heterozygous control littermates. GDF-5 deficient Achilles tendons were structurally weaker than controls, and structural strength differences appe ared to be caused by compromised material properties: after normalizing by collagen per unit length, mutant tendons were still 50% weaker (P < 0.0001) and 50% more compliant (P < 0.001) than controls. Despite comparable level s of skeletal maturity in the two cohorts, the majority of mutant tendon fa ilures occurred in the mid-substance of the tendon (64% of all failures), w hereas the majority of control failures occurred via avulsion (92% of all f ailures). Mutant Achilles tendons contained 40'%, less collagen per microgr am of DNA when compared to controls (P = 0.004). No significant difference in glycosaminoglycan (GAC)/DNA was detected. Ultrastructural analyses indic ated a slight trend toward increased frequency of small diameter (30-100 nm ) collagen fibrils in the mutant Achilles. Our findings suggest that increa sed tendon and ligament laxity may be the cause of the joint dislocations s een in patients with Hunter-Thompson and Grebe type dysplasia, rather than developmental abnormalities in the joints themselves. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.