Journal of Molecular Signaling Updates

Journal of Molecular Signaling Updates - Volume 1

Diminished Genomics Signaling of Extravascular Coagulation and Fibrinolysis in Human Osteoarthritis (OA)-Affected Cartilage

Published on: 25 March 2016

Pages: 41-50

Shaily A. Amin1and Abul B.M.M.K Islam2

1Department of Medicine, Medical University of Silesia, 40-752 Katowice, Poland and 2Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka 1000, Bangladesh

Abstract: Human osteoarthritis (OA) is a degenerative joint disease, which exhibits upregulation and activation of coagulation-fibrinolysis (C-F) cascade in blood, synovial tissue, and fluid. It remains unclear if the primary target cells (chondrocytes) in cartilage contribute to the pool of extravascular C-F components and may add to signal transduction involving "covert inflammation" and / or matrix depletion in human OA-affected cartilage. We isolated and purified total RNA directly from normal and OA-affected cartilage. We utilized a sensitive method of gene chips and gene expression array, whichidentified and quantitated mRNA signals representing the C-F system in normal and OA-affected cartilage.Bioinformatics and statistical software annotated the heat maps and interactome representing the differentially expressed mRNA in normal and OA-affected cartilage. There was a significant (p ≤ 0.05) decrease ingene expression of the multifunctionalcoagulation factor FXIIIA1in OA-affected cartilage, which can have a profound effect on mineralization, cross-linking of extracellular matrix components, matrix depletion, and integrity of cartilage. Furthermore, the pathophysiological environment in human OA-affected cartilage showed suppression of gene expression signaling of C-F-related genes via a significant (p ≤ 0.05) increase in gene expressionof inhibitory proteases (e.g., SERPINE1, SERPINA5, andPROS1) that are known to block the activity of C-F cascades irreversibly. Additionally, other serpins (SERPINH1, SERPINF1 or SERPING1) whose genetic defects also exhibit detrimental effects on cartilage homeostasis were also observed to be significantly (p ≤ 0.05) modulated in human OA-affected cartilage. One of the previously unknown characteristics of the pathophysiology of human OA-affected cartilage was the downregulationof FXIIIA1 and upregulationof genomicsignaling by serpins. In summary, the increased activity of C-F inhibitors (serpins) inOA-affected cartilage may not directly influence "covert inflammation", but the altered gene expression and signaling may affect matrix depletion in human OA-affected cartilage. Furthermore, the significant shift in the signaling by serpins may play a critical role in chondrocyte development and cartilage homeostasis during cartilage repair and “covert inflammation” in OA.

Keywords: Coagulation, Cartilage, Osteoarthritis, SERPINS, Inflammation.

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