Sikes Katie J, Li Jun, Gao Shu-Guang, Shen Quan, Sandy John D, Plaas Anna, Wang Vincent M
a Department of Orthopedic Surgery , Rush University Medical Center , Chicago , IL , USA.
b Department of Bioengineering , University of Illinois at Chicago , Chicago , IL , USA.
Connect Tissue Res. 2018 Sep;59(5):458-471. doi: 10.1080/03008207.2018.1439483. Epub 2018 Jun 6.
Purpose/Aim of the study: Healthy tendons are maintained in homeostasis through controlled usage of glucose for energy and redox equilibrium. Tendon cell stress imposed by overuse injury or vascular insufficiency is accompanied by activation of wound healing pathways which facilitate an adaptive response and the restoration of homeostasis. To understand this response at the gene expression level we have studied the in vivo effects of injected TGF-β1 in a murine model of tendinopathy, as well as treatment of murine tendon explants with either TGF-β1 or hypoxia in vitro.
We provide evidence (from expression patterns and immunohistochemistry) that both in vivo and in vitro, the stress response in tendon cells may be metabolically controlled in part by glycolytic reprogramming. A major feature of the response to TGF-β1 or hypoxia is activation of the Warburg pathway which generates lactate from glucose under normoxia and thereby inhibits mitochondrial energy production.
We discuss the likely outcome of this major metabolic shift in terms of the potential benefits and damage to tendon and suggest how incorporation of this metabolic response into our understanding of initiation and progression of tendinopathies may offer new opportunities for diagnosis and the monitoring of therapies.
研究目的：健康的肌腱通过对葡萄糖的能量利用和氧化还原平衡的控制来维持体内稳态。过度使用损伤或血管功能不全所施加的肌腱细胞应激伴随着伤口愈合途径的激活，这有助于适应性反应和体内稳态的恢复。为了在基因表达水平上理解这种反应，我们研究了在肌腱病小鼠模型中注射转化生长因子-β1（TGF-β1）的体内效应，以及在体外用TGF-β1或缺氧处理小鼠肌腱外植体的情况。
我们提供了证据（来自表达模式和免疫组织化学）表明，在体内和体外，肌腱细胞中的应激反应可能部分受糖酵解重编程的代谢控制。对TGF-β1或缺氧反应的一个主要特征是Warburg途径的激活，该途径在常氧下从葡萄糖产生乳酸，从而抑制线粒体能量产生。
我们从对肌腱的潜在益处和损害方面讨论了这种主要代谢转变可能的结果，并提出将这种代谢反应纳入我们对肌腱病发生和进展的理解中如何可能为诊断和治疗监测提供新的机会。
