title: Impact of TGF-β inhibition during acute exercise on Achilles tendon extracellular matrix.
abstract: The purpose of this study was to evaluate the role of TGF-β1in regulating tendon extracellular matrix after acute exercise. Wistar rats exercised (n = 15) on a treadmill for four consecutive days (60 min/day) or maintained normal cage activity. After each exercise bout, the peritendinous space of each Achilles tendon was injected with a TGF-β1receptor inhibitor or sham. Independent of group, tendons injected with inhibitor exhibited ~50% lower Smad 3 (Ser423/425) (P < 0.05) and 2.5-fold greater ERK1/2 phosphorylation (P < 0.05) when compared with sham (P < 0.05). Injection of the inhibitor did not alter collagen content in either group (P > 0.05). In exercised rats, hydroxylyslpyridinoline content and collagen III expression were lower (P < 0.05) in tendons injected with inhibitor when compared with sham. In nonexercised rats, collagen I and lysyl oxidase (LOX) expression was lower (P < 0.05) in tendons injected with inhibitor when compared with sham. Decorin expression was not altered by inhibitor in either group (P > 0.05). On the basis of evaluation of hematoxylin and eosin (H&E) stained cross sections, cell numbers were not altered by inhibitor treatment in either group (P > 0.05). Evaluation of H&E-stained sections revealed no effect of inhibitor on collagen fibril morphology. In contrast, scores for regional variation in cellularity decreased in exercised rats (P < 0.05). No differences in fiber arrangement, structure, and nuclei form were noted in either group (P > 0.05). Our findings suggest that TGF-β1signaling is necessary for the regulation of tendon cross-link formation, as well as collagen and LOX gene transcription in an exercise-dependent manner.
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona.
authors.forename: Ross M
authors.initials: RM
authors.lastname: Potter
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona.|Department of Basic Medical Sciences, University of Arizona, College of Medicine-Phoenix, Phoenix, Arizona.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Huynh
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona.|Department of Basic Medical Sciences, University of Arizona, College of Medicine-Phoenix, Phoenix, Arizona.
authors.forename: Brent D
authors.initials: BD
authors.lastname: Volper
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Arthur
authors.affiliation: Arizona State University, School of Nutrition and Health Promotion, Healthy Lifestyles Research Center, Exercise Science and Health Promotion, Phoenix, Arizona.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: D'Lugos
authors.affiliation: Musculoskeletal Rehabilitation Research Unit & Institute of Sports Medicine Copenhagen Bispebjerg Hospital Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: Mikkel A
authors.initials: MA
authors.lastname: Sørensen
authors.affiliation: Musculoskeletal Rehabilitation Research Unit & Institute of Sports Medicine Copenhagen Bispebjerg Hospital Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: S Peter
authors.initials: SP
authors.lastname: Magnusson
authors.affiliation: Arizona State University, School of Nutrition and Health Promotion, Healthy Lifestyles Research Center, Exercise Science and Health Promotion, Phoenix, Arizona.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Dickinson
authors.affiliation: Department of Basic Medical Sciences, University of Arizona, College of Medicine-Phoenix, Phoenix, Arizona.
authors.forename: Taben M
authors.initials: TM
authors.lastname: Hale
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona; carrol71@purdue.edu.|Department of Health and Kinesiology, Purdue University, West Lafayette, Indiana.
authors.forename: Chad C
authors.initials: CC
authors.lastname: Carroll
mesh_terms: D000125:Achilles Tendon / Q000502:physiology*; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism*; D005109:Extracellular Matrix / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D008297:Male; D010805:Physical Conditioning, Animal / Q000379:methods*; D005082:Physical Exertion / Q000502:physiology; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D008249:Protein-Lysine 6-Oxidase
keywords: TGF-β1; collagen; cross-linking; exercise; tendon