Choi Woo Jin, Park Min Sung, Park Kwang Hwan, Courneya Jean-Paul, Cho Jin Sun, Schon Lew C, Lee Jin Woo
Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, South Korea.
Texas A&M Health Science Center College of Medicine, Institute for Regenerative Medicine, Temple, TX, USA.
Foot Ankle Int. 2014 Oct;35(10):1045-56. doi: 10.1177/1071100714540885. Epub 2014 Jun 23.
Tendinopathy is a clinical problem for which treatment shows mixed results and treatment options are limited. Gene expression signatures early in the mechanotransduction pathway can accurately predict risk and correlate with different clinical outcomes. Studies aimed at elucidating the molecular mechanisms of tendinopathy have focused on small cohorts of genes that show an incomplete picture of the degeneration process. This study compared the effect of cyclic strain on gene expression in tendon cells from normal tendon and chronically painful areas of tendinopathy in 3 patients.
We measured a panel of mechanotransduction genes and cytoskeletal tensional balance with and without cyclic strain, which disrupts connective tissue synthetic-degradative equilibrium. Normal and degenerative tendons were obtained from patients undergoing surgery to treat chronic painful tendinopathy. A cyclic strain model was established to measure cytoskeletal tensional homeostasis.
Prior to cyclic strain, the normal tendon cells exhibited varying patterns of elevated expression of 7 genes compared with degenerative tendon cells. In response to cyclic strain, gene expression of COL1A1, ITGA6, CTNNA1, and CLEC3B was up-regulated in normal tendon cells. Cyclic strain had no effect on degenerative tendon cells. Cyclic strain exacerbated the inhibition of protein synthesis in both cell types, especially in the degenerative tendon cells.
Alterations in the pattern of gene expression are suggestive of a dynamic equilibrium between synthesis and degradation, whereby cell adhesion molecules are predominantly up-regulated to facilitate cellular reorientation in response to their altered functional environment.
These data might have future applications, including the identification of markers for early diagnosis, targets for drug design, and indicators for treatment responsiveness and prognosis.
肌腱病是一个临床问题，其治疗效果参差不齐且治疗选择有限。机械转导途径早期的基因表达特征能够准确预测风险并与不同的临床结果相关联。旨在阐明肌腱病分子机制的研究主要集中在一小部分基因上，这些研究对退变过程的描述并不完整。本研究比较了循环应变对3例患者正常肌腱和慢性疼痛性肌腱病区域的肌腱细胞基因表达的影响。
我们测量了一组机械转导基因以及在有和无循环应变情况下的细胞骨架张力平衡，循环应变会破坏结缔组织的合成 - 降解平衡。正常和退变的肌腱取自接受手术治疗慢性疼痛性肌腱病的患者。建立循环应变模型以测量细胞骨架张力稳态。
在施加循环应变之前，与退变的肌腱细胞相比，正常肌腱细胞中有7个基因呈现出不同的表达升高模式。在循环应变的作用下，正常肌腱细胞中COL1A1、ITGA6、CTNNA1和CLEC3B的基因表达上调。循环应变对退变的肌腱细胞没有影响。循环应变加剧了两种细胞类型中蛋白质合成的抑制，尤其是在退变的肌腱细胞中。
基因表达模式的改变提示了合成与降解之间的动态平衡，即细胞黏附分子主要上调以促进细胞在功能环境改变时的重新定向。
这些数据可能具有未来应用价值，包括早期诊断标志物的识别、药物设计靶点以及治疗反应性和预后指标。
