Impact of TGF-β inhibition during acute exercise on Achilles tendon extracellular matrix

TY - JOUR

T1 - Impact of TGF-β inhibition during acute exercise on Achilles tendon extracellular matrix

AU - Potter, Ross M

AU - Huynh, Richard T

AU - Volper, Brent D

AU - Arthur, Kathryn A

AU - D'Lugos, Andrew C

AU - Sørensen, Mikkel A

AU - Magnusson, S Peter

AU - Dickinson, Jared M

AU - Hale, Taben M

AU - Carroll, Chad C

N1 - Copyright © 2017 the American Physiological Society.

PY - 2017

Y1 - 2017

N2 - The purpose of this study was to evaluate the role of TGF-ß1 in 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-ß1 receptor 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-ß1 signaling is necessary for the regulation of tendon cross-link formation, as well as collagen and LOX gene transcription in an exercisedependent manner.

AB - The purpose of this study was to evaluate the role of TGF-ß1 in 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-ß1 receptor 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-ß1 signaling is necessary for the regulation of tendon cross-link formation, as well as collagen and LOX gene transcription in an exercisedependent manner.

KW - Achilles Tendon/physiology

KW - Animals

KW - Collagen Type I/metabolism

KW - Extracellular Matrix/physiology

KW - Extracellular Matrix Proteins/metabolism

KW - Male

KW - Physical Conditioning, Animal/methods

KW - Physical Exertion/physiology

KW - Protein-Lysine 6-Oxidase/metabolism

KW - Rats

KW - Rats, Wistar

KW - Transforming Growth Factor beta1/antagonists & inhibitors

U2 - 10.1152/ajpregu.00439.2016

DO - 10.1152/ajpregu.00439.2016

M3 - Journal article

C2 - 27927626

SN - 0363-6119

VL - 312

SP - R157-R164

JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology

JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology

IS - 1

ER -