Date of Award

Spring 5-2020

Author's School

McKelvey School of Engineering

Author's Department

Biomedical Engineering

Degree Name

Master of Science (MS)

Degree Type

Thesis

Abstract

Osteoarthritis (OA), as the most common form of arthritis and a leading cause of disability worldwide, currently has no disease-modifying drugs. Inflammation plays an important role in cartilage degeneration in OA, and pro-inflammatory cytokines, IL-1β and TNF-α, have been shown to induce degradative changes along with aberrant gene expression in chondrocytes, the only resident cells in cartilage. The goal of this study was to further understand the transcriptomic regulation of tissue-engineered cartilage in response to inflammatory cytokines using an in vitro miPSC model system. We performed RNA sequencing for the IL-1β or TNF-α treated tissue-engineered cartilage derived from murine iPSCs, and analyzed transcriptomic profiles by comparing with those of two different osteoarthritis models and human OA cartilage samples. We investigated differentially expressed genes (DEGs) as well as gene set enrichment and protein-protein interaction network, showing a significant similarity between model systems and human OA cartilage. Our analysis revealed a significant number of overlapping DEGs, together with consistent pathway enrichment in inflammatory response, cytokine-mediated response and extracellular matrix organization, which support that the murine iPSC model system can replicate many of the characteristics of OA cartilage at the transcriptomic level, specifically in the catabolic aspect of inflammation induce OA. The murine iPSC model system provides a method for studying the pro-inflammatory response and pathogenesis in OA cartilage and will be a valuable dataset for identifying therapeutic targets of inflammation-induced OA.

Language

English (en)

Chair

Farshid Guilak

Committee Members

Farshid Guilak Bo Zhang Kareem Azab

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