Sexual dimorphism in the effect of GDF-6 deficiency on murine tendon

Three members of the growth/differentiation factor (GDF) subfamily of bone morphogenetic proteins (BMPs), GDFs-5, -6, and -7, have demonstrated the potential to augment tendon and ligament repair. To gain further insight into the in vivo role of these molecules, previous studies have characterized intact and healing tendons in mice with functional null mutations in GDF-5 and -7. The primary goal of the present study was to perform a detailed characterization of the intact tendon phenotype in 4- and 16-week-old male and female GDF6-/- mice and their +/+ littermates. The results demonstrate that GDF6 deficiency was associated with an altered tendon phenotype that persisted into adulthood. Among males, GDF6-/- tail tendon fascicles had significantly less collagen and glycosaminoglycan content, and these compositional differences were associated with compromised material properties. The effect of GDF6 deficiency on tendon was sexually dimorphic, however, for among female GDF6-/- mice, neither differences in tendon composition nor in material properties were detected. The tendon phenotype that was observed in males appeared to be stronger in the tail site than in the Achilles tendon site, where some compositional differences were present, but no material property differences were detected. These data support existing in vitro studies, which suggest a potential role for BMP-13 (the human homologue to GDF-6) in tendon matrix modeling and/or remodeling.