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

Ross M. Potter, Richard T. Huynh, Brent D. Volper, Kathryn A. Arthur, Andrew C. D’Lugos, Mikkel A. Sørensen, S. Peter Magnusson, Jared Dickinson, Taben M. Hale, Chad C. Carroll

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    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)R157-R164
    JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
    Volume312
    Issue number1
    DOIs
    StatePublished - Jan 1 2017

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    Keywords

    • Collagen
    • Cross-linking
    • Exercise
    • TGF-ß
    • Tendon

    ASJC Scopus subject areas

    • Physiology
    • Physiology (medical)

    Cite this

    Potter, R. M., Huynh, R. T., Volper, B. D., Arthur, K. A., D’Lugos, A. C., Sørensen, M. A., Peter Magnusson, S., Dickinson, J., Hale, T. M., & Carroll, C. C. (2017). Impact of TGF-β inhibition during acute exercise on achilles tendon extracellular matrix. American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 312(1), R157-R164. https://doi.org/10.1152/ajpregu.00439.2016