TY - JOUR
T1 - GDF-5 deficiency in mice delays Achilles tendon healing
AU - Chhabra, A.
AU - Tsou, D.
AU - Clark, R. T.
AU - Gaschen, V.
AU - Hunziker, E. B.
AU - Mikic, B.
N1 - Funding Information:
We would like to thank Dr. Rashard Dacus, M.D. for his assistance with the histomorphometric analyses, and Dr. Gary Balian, Ph.D. for helpful discussion. This work was funded in part by a grant from the NIH to BM (AR45828).
PY - 2003
Y1 - 2003
N2 - The aim of this study was to examine the role of one of the growth/differentiation factors, GDF-5, in the process of tendon healing. Specifically, we tested the hypothesis that GDF-5 deficiency in mice would result in delayed Achilles tendon repair. Using histologic, biochemical, and ultrastructural analyses, we demonstrate that Achilles tendons from 8-week-old male GDF-5 -/- mice exhibit a short-term delay of 1-2 weeks in the healing process compared to phenotypically normal control littermates. Mutant animals took longer to achieve peak cell density, glycosaminoglycan content, and collagen content in the repair tissue, and the time course of changes in collagen fibril size was also delayed. Revascularization was delayed in the mutant mice by 1 week. GDF-5 deficient Achilles tendons also contained significantly more fat within the repair tissue at all time points examined, and was significantly weaker than control tissue at 5 weeks after surgery, but strength differences were no longer detectable by 12-weeks. Together, these data support the hypothesis that GDF-5 may play an important role in modulating tendon repair, and are consistent with previously posited roles for GDF-5 in cell recruitment, migration/adhesion, differentiation, proliferation, and angiogenesis.
AB - The aim of this study was to examine the role of one of the growth/differentiation factors, GDF-5, in the process of tendon healing. Specifically, we tested the hypothesis that GDF-5 deficiency in mice would result in delayed Achilles tendon repair. Using histologic, biochemical, and ultrastructural analyses, we demonstrate that Achilles tendons from 8-week-old male GDF-5 -/- mice exhibit a short-term delay of 1-2 weeks in the healing process compared to phenotypically normal control littermates. Mutant animals took longer to achieve peak cell density, glycosaminoglycan content, and collagen content in the repair tissue, and the time course of changes in collagen fibril size was also delayed. Revascularization was delayed in the mutant mice by 1 week. GDF-5 deficient Achilles tendons also contained significantly more fat within the repair tissue at all time points examined, and was significantly weaker than control tissue at 5 weeks after surgery, but strength differences were no longer detectable by 12-weeks. Together, these data support the hypothesis that GDF-5 may play an important role in modulating tendon repair, and are consistent with previously posited roles for GDF-5 in cell recruitment, migration/adhesion, differentiation, proliferation, and angiogenesis.
KW - Bone morphogenetic protiens
KW - GDF-5
KW - Growth/differentiation factors
KW - Mouse
KW - Tendon repair
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U2 - 10.1016/S0736-0266(03)00049-4
DO - 10.1016/S0736-0266(03)00049-4
M3 - Article
C2 - 12919870
AN - SCOPUS:0042889115
SN - 0736-0266
VL - 21
SP - 826
EP - 835
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
IS - 5
ER -