Alpha-2 adrenergic stimulation triggers Achilles tenocyte hypercellularity: Comparison between two model systems

Authors

  • L. J. Backman,

    1. Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden
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  • G. Andersson,

    1. Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden
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  • G. Fong,

    1. Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden
    2. Department of Physical Therapy, University of British Columbia, Vancouver, British Columbia, Canada
    3. Centre for Hip Health and Mobility, Vancouver Coastal Health and Research Institute, Vancouver, British Columbia, Canada
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  • H. Alfredson,

    1. Department of Surgical and Perioperative Sciences, Sports Medicine, Umeå University, Umeå, Sweden
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  • A. Scott,

    1. Department of Physical Therapy, University of British Columbia, Vancouver, British Columbia, Canada
    2. Centre for Hip Health and Mobility, Vancouver Coastal Health and Research Institute, Vancouver, British Columbia, Canada
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  • P. Danielson

    Corresponding author
    1. Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden
    • Corresponding author: Patrik Danielson, MD, PhD, Department of Integrative Medical Biology, Anatomy, Umeå University, SE-901 87 Umeå, Sweden. Tel: +46 90 786 58 93, Fax: +46 90 786 67 07, E-mail: patrik.danielson@anatomy.umu.se

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Abstract

The histopathology of tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hypercellularity. The primary tendon cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human tendon cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α2A AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these cells, in both models. The proliferation was inhibited by administration of an α2A AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic cell signaling pathway involving phosphorylation of extracellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α2A AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research.

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