title: Age-related changes in focal adhesions lead to altered cell behavior in tendon fibroblasts.
abstract: During aging the increase in collagen cross-linking and total amount of collagen in tendon leads to a decline in both its flexibility and its ability to heal after injury. Fibroblasts are responsible for the synthesis of the macromolecules that constitute tendonous tissue. The ability of fibroblasts to maintain tissue homeostasis is compromised with increasing age underlying many of the age-related pathologies of the musculoskeletal system. This leads to a slowdown in connective tissue healing. Whether these deficits are due to changes in connective tissue, structure or to changes in tendon fibroblast function is unknown. We show that tendon fibroblasts from old mice have an altered morphology, reduced level of function, and exhibit changes in protein transport, compared to fibroblasts from young mice. The fibroblasts from old mice are not senescent, they are distinct phenotypes. Achilles tendon fibroblasts from old mice have low motility and proliferation, a poorly organised actin cytoskeleton and a different localisation of key focal adhesion proteins compared to the same cells from young mice. Additionally we found more of the protein misfolding indicator protein, GADD 153, in fibroblasts from old tendon. These results indicate that changes in tendon fibroblast function may well explain the age-related decline in tendon healing.
authors.affiliation: Department of Food Science, Royal Veterinary and Agricultural University, Rolighedsvej 30, 1958 Frederiksberg C, Denmark.
authors.forename: Solfrid M
authors.initials: SM
authors.lastname: Arnesen
authors.forename: Moira A
authors.initials: MA
authors.lastname: Lawson
mesh_terms: D000125:Achilles Tendon / Q000166:cytology*; D000375:Aging; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002469:Cell Separation; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism; D022001:Focal Adhesions / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D051419:Paxillin / Q000032:analysis; D016608:Talin / Q000032:analysis; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C497250:Ddit3 protein, mouse; D051419:Paxillin; D016608:Talin; D051742:Transcription Factor CHOP; D051416:Focal Adhesion Protein-Tyrosine Kinases; D001616:beta-Galactosidase