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

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; Extracellular matrix; Inflammatory regulation; Matrix metalloproteinase; RNA sequencing.