Growth/differentiation factors (GDFs) play a significant role in numerous skeletal tissues and processes. Previous work using the brachypod mouse has suggested that GDF-5 affects Achilles tendon composition, ultrastructure, and material behavior, as well as tendon repair. The aim of the present study was to examine the role of a related GDF family member, GDF-7 (BMP-12), in intact tendon by studying the Achilles tendon of genetically engineered knockout mice. Achilles tendons from 16-week-old GDF-7 -/- mice contained 14% less GAG/DNA than did wild type littermates (p = 0.0481), although collagen content was comparable to controls. Quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) results show that GDF-5 was upregulated two-threefold in response to the absence of GDF-7 protein. GDF-6 was also upregulated in knockouts, but to a lesser extent (twofold, p = 0.0013). On an ultrastructural level, GDF-7 deficient Achilles tendons exhibited a shift towards smaller diameter fibrils which resulted in a small but significant reduction in mean fibril diameter (-8%, p = 0.05). GDF-7 deficiency did not noticeably affect the expression of fibrillar collagens (I, III, V) or tendon proteoglycans (decorin, fibromodulin, lumican, biglycan, versican, aggrecan). Differences in tendon composition and ultrastructure were not biologically significant enough to have a noticeable effect on the structural or material behavior of the tendons. These results demonstrate that GDF-7 deficiency has a subtle effect on the composition and ultrastructure of murine Achilles tendon. The small magnitude of the observed differences may be due to overcompensation by related GDF family members.
Copyright 2006 Orthopaedic Research Society