Department of Integrative Medical Biology, Anatomy, Umeå University, Umeå, Sweden.
Scand J Med Sci Sports. 2013 Dec;23(6):687-96. doi: 10.1111/j.1600-0838.2011.01442.x. Epub 2012 Jan 31.
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.
患有疼痛性肌腱病的肌腱的组织病理学通常为肌腱病，这是一种发病机制不明的纤维样病变，其组织变化包括细胞增生。已经表明主要的肌腱细胞（腱细胞）表达肾上腺素能受体（主要为α-2A）以及儿茶酚胺产生的标志物，尤其是在肌腱病中。已知肾上腺素能刺激可以诱导其他细胞增殖。本研究在建立的体内跟腱腱病模型（兔）以及体外人肌腱细胞培养模型中，研究了外源性给予α-2 肾上腺素能激动剂的作用。儿茶酚胺产生酶酪氨酸羟化酶和α-2A-肾上腺素能受体（α2AAR）由腱细胞表达，并且在这两种模型中，α-2 肾上腺素能刺激对这些细胞具有增殖作用。增殖被α2AAR 拮抗剂的给药所抑制，并且体外模型进一步表明，增殖性α2A 效应是通过涉及细胞外信号调节激酶 1 和 2 的磷酸化的有丝分裂细胞信号通路介导的。结果表明，肌腱病中腱细胞产生的儿茶酚胺可能通过刺激α2AAR 导致病理的增殖性质，为未来的治疗指明了新的靶标。该研究进一步表明，并非所有方面的研究都需要动物模型。
