Heterogeneous muscle gene expression patterns in patients with massive rotator cuff tears.
Heterogeneous muscle gene expression patterns in patients with massive rotator cuff tears.
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DOI：
10.1371/journal.pone.0190439
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Ward SR
中科院分区：
文献类型：
--
作者：
Gibbons MC;Fisch KM;Pichika R;Cheng T;Engler AJ;Schenk S;Lane JG;Singh A;Ward SR
肩袖 (RC) 肌肉的组成和功能的有害变化是 RC 疾病进展的标志。先前的研究已经证明晚期 RC 疾病中会出现萎缩性和退行性肌肉损失。然而，基因表达和 RC 肌肉病理学之间的关系仍然不清楚，这在很大程度上是由于缺乏将基因表达与组织组成相关联的研究。因此，本研究的目的是确定接受反向肩关节置换术 (RSA) 的患者肌肉活检中组织成分与基因表达的关系。在 40 个 RC 肌肉活检中测量了与肌肉生成、萎缩和细胞死亡、脂肪生成和代谢、炎症和纤维化相关的基因表达，其中包括来自具有可用组织学数据的反向肩关节置换术 (RSA) 病例的 31 个活检和来自完整 RC 肌腱患者的 9 个对照活检。对参考基因进行归一化后，使用线性回归来确定基因表达和组织组成之间的关系。层次聚类和主成分分析（PCA）识别了独特的簇，并使用倍数变化分析来确定簇之间表达的显着差异。我们发现基因表达谱在很大程度上取决于肌肉的存在，肌肉分数是线性回归与基因表达显着相关的唯一组织学参数。类似地，具有组织学证实的肌肉的样品与没有肌肉的样品明显分离。然而，含有肌肉的 RSA 活检中的两个亚组提示了不同的疾病阶段，一组表达萎缩和再生标记，另一组与对照活检或缺乏肌肉的活检没有显着差异。总之，这项研究为解释异质和退化肌肉中的基因表达提供了背景，并为人类 RC 疾病的不同阶段提供了进一步的证据。
Detrimental changes in the composition and function of rotator cuff (RC) muscles are hallmarks of RC disease progression. Previous studies have demonstrated both atrophic and degenerative muscle loss in advanced RC disease. However, the relationship between gene expression and RC muscle pathology remains poorly defined, in large part due to a lack of studies correlating gene expression to tissue composition. Therefore, the purpose of this study was to determine how tissue composition relates to gene expression in muscle biopsies from patients undergoing reverse shoulder arthroplasty (RSA). Gene expression related to myogenesis, atrophy and cell death, adipogenesis and metabolism, inflammation, and fibrosis was measured in 40 RC muscle biopsies, including 31 biopsies from reverse shoulder arthroplasty (RSA) cases that had available histology data and 9 control biopsies from patients with intact RC tendons. After normalization to reference genes, linear regression was used to identify relationships between gene expression and tissue composition. Hierarchical clustering and principal component analysis (PCA) identified unique clusters, and fold-change analysis was used to determine significant differences in expression between clusters. We found that gene expression profiles were largely dependent on muscle presence, with muscle fraction being the only histological parameter that was significantly correlated to gene expression by linear regression. Similarly, samples with histologically-confirmed muscle distinctly segregated from samples without muscle. However, two sub-groups within the muscle-containing RSA biopsies suggest distinct phases of disease, with one group expressing markers of both atrophy and regeneration, and another group not significantly different from either control biopsies or biopsies lacking muscle. In conclusion, this study provides context for the interpretation of gene expression in heterogeneous and degenerating muscle, and provides further evidence for distinct stages of RC disease in humans.
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