Muscle Gene Expression Patterns in Human Rotator Cuff Pathology

Muscle Gene Expression Patterns in Human Rotator Cuff Pathology
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DOI:
10.2106/jbjs.m.01585
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发表时间:
2014-09-17
影响因子:
5.3
通讯作者:
Ward, Samuel R.
Ward, Samuel R.
中科院分区:
医学1区
文献类型:
--
作者:
Choo, Alexander;McCarthy, Meagan;Ward, Samuel R.

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背景:肩袖病理是肩关节疼痛的常见原因,其病因和病理解剖特征各不相同。脂肪浸润、肌肉萎缩和纤维化的病理过程都被认为是肩袖撕裂修复术后不良结局的原因。本研究的目的是测量与脂肪生成、肌生成和纤维化相关的关键基因在人肩袖肌肉损伤后的表达,并比较肩袖病理学不同严重程度患者组之间的表达。方法:冈上肌活检标本来自以下手术组的27名患者,滑囊炎(n = 10)、肌腱病(n = 7)、全层肩袖撕裂(n = 8)和大块肩袖撕裂(n = 2)。定量聚合酶链反应(qPCR)进行表征基因表达途径参与肌生成,脂肪形成,和fibrosis.Results:患者与一个巨大的撕裂表现出下调的纤维形成,脂肪形成,和生肌基因,这表明肌肉是不是在一个积极的变化状态,并可能难以响应刺激。全层撕裂的患者表现出纤维化和脂肪形成基因的上调;在组织水平上,这些对应于对手术修复结果最有害的病理。滑囊炎或tendinopathy的患者仍然表达肌源性基因,表明肌肉可能试图容纳的肌腱tear.Conclusions引起的机械缺陷:基因表达在人类肩袖肌肉肌腱损伤的严重程度不同。滑囊炎和肌腱病患者似乎表达促肌生成基因,而全层撕裂患者则表达与脂肪萎缩和纤维化相关的基因。相比之下,大面积撕裂的患者似乎除了抑制肌生成外,所有基因程序都下调。
Background: Rotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff tear repair. The aims of this study were to measure the expression of key genes associated with adipogenesis, myogenesis, and fibrosis in human rotator cuff muscle after injury and to compare the expression among groups of patients with varied severities of rotator cuff pathology.Methods: Biopsies of the supraspinatus muscle were obtained arthroscopically from twenty-seven patients in the following operative groups: bursitis (n = 10), tendinopathy (n = 7), full-thickness rotator cuff tear (n = 8), and massive rotator cuff tear (n = 2). Quantitative polymerase chain reaction (qPCR) was performed to characterize gene expression pathways involved in myogenesis, adipogenesis, and fibrosis.Results: Patients with a massive tear demonstrated downregulation of the fibrogenic, adipogenic, and myogenic genes, indicating that the muscle was not in a state of active change and may have difficulty responding to stimuli. Patients with a full-thickness tear showed upregulation of fibrotic and adipogenic genes; at the tissue level, these correspond to the pathologies most detrimental to outcomes of surgical repair. Patients with bursitis or tendinopathy still expressed myogenic genes, indicating that the muscle may be attempting to accommodate the mechanical deficiencies induced by the tendon tear.Conclusions: Gene expression in human rotator cuff muscles varied according to tendon injury severity. Patients with bursitis and tendinopathy appeared to be expressing pro-myogenic genes, whereas patients with a full-thickness tear were expressing genes associated with fatty atrophy and fibrosis. In contrast, patients with a massive tear appeared to have downregulation of all gene programs except inhibition of myogenesis.