Publication:


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 (α(2A) 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 α(2A) 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 α(2A) 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.

© 2012 John Wiley & Sons A/S.

Related Articles
Immunohistochemical and in situ hybridization observations favor a local catecholamine production in the human Achilles tendon.
Histol Histopathol. 2008
Immunohistochemical and in situ hybridization observations favor a local catecholamine production in the human Achilles tendon.
Bjur D, Danielson P, Alfredson H, Forsgren S. Histol Histopathol. 2008 Feb; 23(2):197-208.
Studies on the importance of sympathetic innervation, adrenergic receptors, and a possible local catecholamine production in the development of patellar tendinopathy (tendinosis) in man.
Microsc Res Tech. 2007
Studies on the importance of sympathetic innervation, adrenergic receptors, and a possible local catecholamine production in the development of patellar tendinopathy (tendinosis) in man.
Danielson P, Alfredson H, Forsgren S. Microsc Res Tech. 2007 Apr; 70(4):310-24.
Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation.
PLoS One. 2011
Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation.
Backman LJ, Fong G, Andersson G, Scott A, Danielson P. PLoS One. 2011; 6(11):e27209. Epub 2011 Nov 1.
Review The role of vasculature and angiogenesis for the pathogenesis of degenerative tendons disease.
Scand J Med Sci Sports. 2005
Review The role of vasculature and angiogenesis for the pathogenesis of degenerative tendons disease.
Pufe T, Petersen WJ, Mentlein R, Tillmann BN. Scand J Med Sci Sports. 2005 Aug; 15(4):211-22.
Review Position statement. Part one: Immune function and exercise.
Exerc Immunol Rev. 2011
Review Position statement. Part one: Immune function and exercise.
Walsh NP, Gleeson M, Shephard RJ, Gleeson M, Woods JA, Bishop NC, Fleshner M, Green C, Pedersen BK, Hoffman-Goetz L, et al. Exerc Immunol Rev. 2011; 17:6-63.