MicroRNAs Associated with Shoulder Tendon Matrisome Disorganization in Glenohumeral Arthritis.
MicroRNAs Associated with Shoulder Tendon Matrisome Disorganization in Glenohumeral Arthritis.
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DOI：
10.1371/journal.pone.0168077
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Agrawal DK
中科院分区：
文献类型：
--
作者：
Thankam FG;Boosani CS;Dilisio MF;Dietz NE;Agrawal DK
细胞外基质（ECM）为细胞和组织的结构发育提供了核心支持。ECM在许多病理状况中的作用已经得到充分确立，并且已经确定了导致严重后果的ECM相关异常。尽管已经对ECM在软组织相关病理中的作用进行了大量探索，但对其在肌腱炎性疾病中的作用知之甚少。在这项研究中，我们在人肩肱二头肌肌腱的长头中进行了microRNA（miRNA）表达分析，以确定在盂肱关节炎患者的炎症过程中表达改变的关键基因。我们确定了基质金属蛋白酶（MMPs）的差异调节，这可能是在肌腱病变的胶原类型的替代至关重要。miRNA谱显示了各组之间一致的结果，并揭示了炎症肌腱中7种不同miRNA表达的显著变化。有趣的是，所有这七种miRNAs先前都被报道在调节其他病理性疾病中的ECM组织中具有直接或间接作用。此外，还发现这些miRNA改变MMP的表达水平，MMP是与ECM相关异常和病理相关的关键基质降解酶。据我们所知，这是第一份鉴定肌腱中与炎症和基质重组相关的特异性miRNAs的报告。此外，这些发现还支持这些miRNAs在炎症期间改变肌腱中胶原类型比例的潜在作用，这伴随着MMP的差异表达。
The extracellular matrix (ECM) provides core support which is essential for the cell and tissue architectural development. The role of ECM in many pathological conditions has been well established and ECM-related abnormalities leading to serious consequences have been identified. Though much has been explored in regards to the role of ECM in soft tissue associated pathologies, very little is known about its role in inflammatory disorders in tendon. In this study, we performed microRNA (miRNA) expression analysis in the long head of the human shoulder biceps tendon to identify key genes whose expression was altered during inflammation in patients with glenohumeral arthritis. We identified differential regulation of matrix metalloproteinases (MMPs) that could be critical in collagen type replacement during tendinopathy. The miRNA profiling showed consistent results between the groups and revealed significant changes in the expression of seven different miRNAs in the inflamed tendons. Interestingly, all of these seven miRNAs were previously reported to have either a direct or indirect role in regulating the ECM organization in other pathological disorders. In addition, these miRNAs were also found to alter the expression levels of MMPs, which are the key matrix degrading enzymes associated with ECM-related abnormalities and pathologies. To our knowledge, this is the first report which identifies specific miRNAs associated with inflammation and the matrix reorganization in the tendons. Furthermore, the findings also support the potential role of these miRNAs in altering the collagen type ratio in the tendons during inflammation which is accompanied with differential expression of MMPs.
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