The subfamily of growth/differentiation factors (GDFs) known as GDFs 5,6, and 7 appears to be involved in tendon maintenance and repair, although the precise nature of this role has yet to be elucidated. The aim of the present study was to examine the role of GDF-7 in tendon maintenance by studying tail tendon fascicle gene expression, composition, and material property strain rate dependency in 16-week-old male and female GDF-7 deficient mice. GDF-7 deficiency did not affect the biochemical composition of tail tendon fascicles, nor did it significantly affect the tensile material properties obtained at either slow (5%/s) or fast (50%/s) strain rates. Further, no difference was found between genotypes in the strain rate sensitivity of any tensile material property. Consistent with the compositional analyses, QRT-PCR data did not reveal any differences of twofold or greater in the gene expression levels of collagens I, III, V, nor in the proteoglycans decorin, fibromodulin, lumican, biglycan, versican, or aggrecan. Gdf5 expression was upregulated twofold in GDF-7 deficient tail tendons, and Bmp7 expression was downregulated twofold. No notable differences in expression levels for Bmp1-6 or Gdf6 were detected. GDF-5 protein levels were 50% higher in GDF-7 deficient tail tendon compared to wild type tail tendon. The results of this study support the intriguing possibility that compensation by Gdf-5 may be at least in part responsible for the absence of a strong phenotype in GDF-7 deficient mice. ß
Increasing evidence suggests that the growth/differentiation factors, GDFs 5, 6, and 7 in particular, may play a role in tendon and ligament biology. Mice with genetic mutations in Gdf5 have altered tendon composition and mechanical behavior, whereas animals with functional null mutations in Gdf7 have a more subtle tendon phenotype. The present study demonstrates for the first time that a null mutation in Gdf6 is associated with substantially lower levels of tail tendon collagen content (233%) in 4-week-old male mice, which has direct functional consequences for the mechanical integrity of the tissue (45-50% reduction in material properties). These data support a role for GDF6 in tendon matrix modeling.
The purpose of this study was to compare the osteogenic potential of a synthetic and a demineralized bone matrix (DBM) putty using a cranial defect model in New Zealand white rabbits. Paired, bilateral critical-size defects (10 mm) were prepared in the frontal bones of 12 rabbits and filled with either OsteoSelect DBM Putty or NovaBone calcium-phosphosilicate putty. At days 43 and 91, 6 rabbits were killed and examined via semiquantitative histology and quantitative histomorphometry. Defects filled with the DBM putty were histologically associated with less inflammation and fibrous tissue in the defect and more new bone than the synthetic counterpart at both time points. Histomorphometric analysis revealed that the defects filled with DBM putty were associated with significantly more bone formation at day 43 (70.7% vs 40.7%, P = 0.043) and at day 91 (70.4% vs 39.9%, P = 0.0044). The amount of residual implant was similar for both test groups at each time point.
Three members of the growth/differentiation factor (GDF) subfamily of bone morphogenetic proteins (BMPs), , 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 GDF6À/À mice and their þ/þ littermates. The results demonstrate that GDF6 deficiency was associated with an altered tendon phenotype that persisted into adulthood. Among males, GDF6À/À 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 GDF6À/À 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.
The growth/differentiation factors (GDFs) are a subfamily of bone morphogenetic proteins (BMPs) known to play a role in a variety of skeletal processes. Previous work using the brachypod mouse demonstrated that mice deficient in GDF-5 have long bones with diminished material properties and ash content compared with control littermates. Our aim was to examine the role of a related GDF family member, GDF-7 (BMP-12), in cortical bone by examining the geometric and material contributions to whole bone structural behavior in GDF-7-deficient mice. Femora from 16-week-old GDF-7 -/- animals had significantly smaller bone cross-sectional geometric parameters (e.g., -20% medial/lateral and anterior/posterior moments of inertia). Despite having smaller bone cross-sections, all structural parameters obtained from four-point bending tests were comparable to those of wild-type bones due to elevated cortical bone material properties (+18% modulus of elasticity, +28% yield strength, and +18% ultimate strength). No significant differences in ash content or collagen content were detected, however. These data suggest that GDF-7 deficiency is associated with elevated cortical bone material properties that compensate for decreased geometric properties, thereby preserving bone structural integrity. The compositional and/or microstructural bases for these altered material properties remain to be determined, however.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.