title: Synergist ablation induces rapid tendon growth through the synthesis of a neotendon matrix.
abstract: Mechanical loading can increase tendon cross-sectional area (CSA), but the mechanisms by which this occurs are largely unknown. To gain a greater understanding of the cellular mechanisms of adult tendon growth in response to mechanical loading, we used a synergist ablation model whereby a tenectomy of the Achilles tendon was performed to induce growth of the synergist plantaris tendon. We hypothesized that after synergist ablation progenitor cells in the epitenon would proliferate and increase the size of the existing tendon matrix. Adult male mice were subjected to a bilateral Achilles tenectomy, and plantaris tendons were isolated from mice at 0, 2, 7, 14, and 28 days after surgery. Tendons were sectioned stained with either fast green and hematoxylin, prepared for fluorescent microscopy, or prepared for gene expression of scleraxis and type I collagen. After overload, there was a dramatic increase in total CSA of tendons, whereas the size of the original tendon matrix was not changed. Growth primarily occurred through the formation of a neotendon matrix between the original tendon and the epitenon, and contained cells that were proliferative and scleraxis positive. Additionally, an initial expansion of fibroblast cells occurred before the synthesis of new extracellular matrix. Fibroblasts in the original tendon did not re-enter the cell cycle. The results from this study provide new insight into the mechanisms of tendon growth, indicate tendon consists mostly of postmitotic cells, and that growth of tendon primarily occurs from the most superficial layers outward.
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan and Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Gumucio
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan and.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Phan
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan and.
authors.forename: David G
authors.initials: DG
authors.lastname: Ruehlmann
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan and.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Noah
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan and Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan cmendias@umich.edu.
authors.forename: Christopher L
authors.identifier: http://orcid.org/0000-0002-2384-0171
authors.initials: CL
authors.lastname: Mendias
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D008297:Male; D051379:Mice; D013234:Stem Cells / Q000502:physiology; D013710:Tendons / Q000254:growth & development*; D016474:Weight-Bearing
chemical_list: D024042:Collagen Type I
keywords: neotendon; scleraxis; tendon