The effect of mechanical load on tendinopathic tissue is usually studied in the context of identifying mechanisms responsible for tendon degradation. However, loading is also one of the most common treatments for tendinopathy. It is therefore possible that different loads result in different cellular responses within a tendon. To test this hypothesis, we first established a rodent model of tendinopathy that has a transcriptional signature similar to human tendinopathy. Tendinopathy was modeled in the rat by producing a lesion in the central core of the patellar tendon using a biopsy punch, followed by two weeks to allow scar formation. We performed 3’ Tag RNA-Seq to identify genes that were differentially expressed between the native and scarred rat patellar tendon. Genes involved in extracellular matrix (ECM) structure and turnover were increased, mitochondrial genes were decreased, and there was no inflammatory signature in the tendinopathic tissue. These transcriptional changes phenocopy previously published whole transcriptome analysis in human tendinopathy. After validating the model, the initial response to injury and loading was determined. Two weeks after creation of the patellar tendon lesion, the tendon was loaded using either 4 × 30s isometric or a time-under-tension matched (360 × 0.33s) dynamic protocol. Injured +/- loading and contralateral control tendons were collected eighteen hours after loading, RNA was extracted, and gene expression was quantified using qRT-PCR of the scar with or without loading. The expression of scleraxis and type I collagen increased following isometric loading relative to those loaded dynamically. By contrast, the expression of type II collagen increased in the dynamic samples relative to those loaded isometrically. These data suggest that dynamic loading of a central core tendon injury increases fibrocartilage markers, whereas long isometric loads stimulate markers of tendon regeneration.

通常在确定导致肌腱退化的机制的背景下研究机械负荷对肌腱病变组织的影响。然而，负重也是肌腱病最常见的治疗方法之一。因此，不同的负荷可能导致肌腱内的不同细胞反应。为了验证这一假设，我们首先建立了一种啮齿动物的肌腱病模型，该模型具有与人类肌腱病相似的转录特征。通过使用活检打孔器在髌腱的中央核心处产生损伤，在大鼠中模拟肌腱病，随后两周以允许瘢痕形成。我们进行了 3' Tag RNA-Seq 以鉴定在天然和伤痕累累的大鼠髌腱之间差异表达的基因。参与细胞外基质 (ECM) 结构和周转的基因增加，线粒体基因减少，肌腱病变组织中没有炎症特征。这些转录变化表型以前发表了人类肌腱病的全转录组分析。在验证模型后，确定了对损伤和负荷的初始响应。在创建髌腱损伤两周后，使用 4 × 30s 等距或张力下时间匹配 (360 × 0.33s) 动态协议加载肌腱。加载后 18 小时收集受伤的 +/- 加载和对侧对照肌腱，提取 RNA，并使用有或没有加载的疤痕的 qRT-PCR 量化基因表达。相对于动态加载的等长加载后，巩膜和 I 型胶原蛋白的表达增加。相比之下，相对于等长加载的样品，动态样品中 II 型胶原蛋白的表达增加。这些数据表明，中央核心肌腱损伤的动态负荷增加了纤维软骨标志物，而长等长负荷刺激了肌腱再生的标志物。