Identification of Differentially Expressed Genes Associated with Extracellular Matrix Degradation and Inflammatory Regul
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ORIGINAL RESEARCH
Identification of Differentially Expressed Genes Associated with Extracellular Matrix Degradation and Inflammatory Regulation in Calcific Tendinopathy Using RNA Sequencing Namjoon Cho1 · Sung‑Gwon Lee2 · Jong Ok Kim3 · Yong‑An Kim1 · Eun‑Mi Kim4 · Chungoo Park2 · Jong‑Hun Ji5 · Kee K. Kim1 Received: 6 May 2020 / Accepted: 31 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords Calcific tendinopathy · RNA sequencing · Extracellular matrix · Matrix metalloproteinase · Inflammatory regulation
Introduction Abnormal calcium crystal deposition in human tendon and soft tissues is the cause of various diseases, such as calcific tendinopathy (CT), vascular calcification (VC), and kidney stone [1]. There are various causes of VC, including diabetes and chronic kidney diseases; however, several drugs have Namjoon Cho, Sung-Gwon Lee and Jong Ok Kim have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00223-020-00743-x) contains supplementary material, which is available to authorized users. * Chungoo Park [email protected] * Jong‑Hun Ji [email protected] * Kee K. Kim [email protected] Extended author information available on the last page of the article
been developed for its treatment [2–4]. Kidney stone has relatively mild symptoms, and various non-surgical treatment methods are used to remove it [5]. In contrast, despite the high probability of women developing CT in their 40 s and 50 s, effective non-surgical therapies have not been developed for it, because of the lack of pathological studies as well understanding of the molecular basis of CT [6]. CT is characterized by severe pain, inflammation, and loss of shoulder function due to the calcium hydroxyapatite deposition on the rotator cuff tendon [7]. Further, it can affe
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