Effect of GDF‐7 deficiency on tail tendon phenotype in mice

Abstract

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

Novel Model of Tendon Regeneration Reveals Distinct Cell Mechanisms Underlying Regenerative and Fibrotic Tendon Healing

“…In the context of injury, TGFβ has also been implicated as a potent inducer of fibrosis. While BMP signaling generally inhibits tendon during development (while inducing cartilage), select members of the BMP family (BMPs 12, 13, and 14) may drive tendon differentiation45464748. Future studies will therefore elucidate the specific activities of TGFβ, BMP, and their downstream signaling and interactions in tendon regeneration, fibrosis, and heterotopic ossification.…”

Collagen fibrillogenesis in tendon development: Current models and regulation of fibril assembly

“…However, the role of these growth factors is still unknown. Other growth factors, including FGF-4 and-8 (Edom-Vovard et al, 2001,2002;Schweitzer et al, 2001;Brent et al, 2003), and GDF-5, -6, -7, and -8 (Merino et al, 1999;Clark et al, 2001;Mikic et al, 2001Mikic et al, , 2006Mikic et al, , 2008Mendias et al, 2008), have also been shown to have effects on tendon development. However, their potential roles in collagen fibrillogenesis during tendon development are still being elucidated.…”

Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems

“…The exact cues necessary for the differentiation of progenitor cells along the tendinogenic pathway into tendon fibroblasts is unknown, however, several cytokines such as transforming growth factor – B, basic fibroblast growth factor, insulin growth factor – I, platelet derived growth factor and Growth/Differentiation Factor −5 have been identified as possible participating factors (James et al 2008). Among these, Growth/Differentiation factor −5 stimulates cell growth and modulates the repair process in tendons and ligaments (Chhabra et al 2003, Mikic et al 2001, Mikic et al 2009, Mikic et al 2008). GDF-5 when delivered into ectopic sites in animal models, elicits the formation of neotendinous tissue (Wolfman et al 1997).…”