Identification of Differentially Expressed Genes Associated with Extracellular Matrix Degradation and Inflammatory Regulation in Calcific Tendinopathy Using RNA Sequencing

Identification of Differentially Expressed Genes Associated with Extracellular Matrix Degradation and Inflammatory Regulation in Calcific Tendinopathy Using RNA Sequencing
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DOI:
10.1007/s00223-020-00743-x
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发表时间:
2020-08-09
影响因子:
4.2
通讯作者:
Kim, Kee K.
Kim, Kee K.
中科院分区:
医学3区
文献类型:
--
作者:
Cho, Namjoon;Lee, Sung-Gwon;Kim, Kee K.

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钙化性肌腱病(CT),由于羟基磷灰石钙沉积在肩袖肌腱,主要影响妇女在他们的40和50年代,并导致严重的肩部疼痛。然而,其发病机制的分子基础和适当的治疗方法在很大程度上是未知的。在这项研究中,我们确定了202个差异表达基因(DEG)钙化和邻近正常肌腱组织的肩袖使用RNA测序为基础的转录组分析。DEG在细胞外基质(ECM)降解和炎症相关过程中高度富集。此外,基质金属蛋白酶9(MMP 9)和基质金属蛋白酶13(MMP 13),与ECM降解相关的两种酶,被发现分别高度上调25.85和19.40倍,在钙化肌腱组织相比,相邻的正常肌腱组织。组织学分析表明,胶原降解和巨噬细胞浸润的钙化存款在肩袖肌腱的网站。我们的研究作为一个基础,可能有助于更好地了解与CT相关的发病机制,从而更好地管理疾病。
Calcific tendinopathy (CT), developed due to calcium hydroxyapatite deposition in the rotator cuff tendon, mostly affects women in their 40 s and 50 s and causes severe shoulder pain. However, the molecular basis of its pathogenesis and appropriate treatment methods are largely unknown. In this study, we identified 202 differentially expressed genes (DEGs) between calcific and adjacent normal tendon tissues of rotator cuff using RNA sequencing-based transcriptome analysis. The DEGs were highly enriched in extracellular matrix (ECM) degradation and inflammation-related processes. Further, matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 13 (MMP13), two of the enzymes associated with ECM degradation, were found to be highly upregulated 25.85- and 19.40-fold, respectively, in the calcific tendon tissues compared to the adjacent normal tendon tissues. Histopathological analyses indicated collagen degradation and macrophage infiltration at the sites of calcific deposit in the rotator cuff tendon. Our study acts as a foundation that may help in better understanding of the pathogenesis associated with CT, and thus in better management of the disease.