Publication Date

2015-07-02

Availability

Embargoed

Embargo Period

2017-07-02

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biomedical Engineering (Engineering)

Date of Defense

2015-05-29

First Committee Member

C-Y Charles Huang

Second Committee Member

Lee Kaplan

Third Committee Member

Alicia Jackson

Fourth Committee Member

Liyong Wang

Fifth Committee Member

Herman Cheung

Abstract

Traumatic injury to cartilage has been shown to lead to Post-traumatic Osteoarthritis (PTOA). The acute phase of PTOA is characterized with increased expression of aggrecanases and inflammatory cytokines in the injured cartilage. Aberrant regulation of microRNAs (miRNAs) in the cartilage has been associated with the pathogenesis of PTOA. The objective of this dissertation work was to elucidate potential early detection and intervention strategies for acute knee injury based on the miRNA and genetic changes of knee joint tissues. An ex-vivo intact joint impact injury model was created to examine the miRNA and inflammatory and degenerative gene expression in cartilage and meniscus during the acute phase of injury. Using this model, four potential early intervention treatments for PTOA were compared, and their effects on the early inflammatory and catabolic events after acute cartilage injury were determined at 8 hours after intact joint impact. The time- and concentration-dependent nature of cellular and extracellular miRNAs in chondrocytes, synoviocytes, and meniscus cells as influenced by inflammatory cytokines and the ratio of extracellular miRNA were analyzed as potential indicator of early OA progression. In a proof of concept study, the ratios of synovial fluid miRNAs after acute cartilage injury were examined using the ex-vivo intact joint impact model as potential indicator of acute cartilage injury. A recommendation for further study is enclosed.

Keywords

Post-traumatic osteoarthritis; cartilage; impact injury; microRNA; biomarker; early intervention

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