The Role of MicroRNA-140 and its IsomiRs in an In Vitro model of Osteoarthritis
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AbstractOsteoarthritis (OA) is the most common joint disease. OA is a complex multietiological disease where several factors and drivers are involved. This thesis is focused on inflammation as a driver and a perpetuator of OA. microRNAs (miRNAs) are small RNAs that regulate gene expression. An inflammation induced in vitro model simulating the adverse inflammatory milieu in OA was used and the role of miR-140, its isomiRs and miR-146a were investigated. Using global proteome and transcriptome analysis we revealed how these miRNAs exhibit strong downregulatory effects on key inflammatory mediators. Simultaneously they have the capacity to restore several homeostatic processes that are known to be altered in OA, in addition to stimulating cartilage anabolism and thus help heal the joint. The work presented in this thesis contributes to our understanding of some of the molecular processes that can be manipulated in a favorable manner and reveals more of the therapeutical potential harbored by miRNAs, not only for OA, but also for other immune-related diseases. Gene therapy will be more common in the future, this work may contribute to bringing gene therapy for OA a step closer to reality.
List of papers
|Paper I: Multi-pathway Protective Effects of MicroRNAs on Human Chondrocytes in an In Vitro Model of Osteoarthritis. Rua Nader Al-Modawi, Jan E. Brinchmann, Tommy A. Karlsen. Molecular Therapy-Nucleic acids (2019), Volume 17, Pages 776-790. DOI: 10.1016/j.omtn.2019.07.011. The article is included in the thesis. Also available at: https://doi.org/10.1016/j.omtn.2019.07.011|
|Paper II: Extensive Downregulation of Immune Gene Expression by MicroRNA-140-3p 5' isomiR in an In Vitro Model of Osteoarthritis. Rua Nader Al-Modawi, Jan E. Brinchmann, Tommy A. Karlsen. Manuscript submitted to Molecular Therapy. To be published. The paper is not available in DUO awaiting publishing.|
|Paper III: Immunological Off-target Effects of MicroRNA Control Sequences. Rua Nader Al-Modawi, Jan E. Brinchmann, Tommy A. Karlsen. Manuscript. To be published. The paper is not available in DUO awaiting publishing.|