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Development of a novel 3D human cartilage model system to investigate changes in cartilage associated with osteoarthritis

Heil, Andreas 2015. Development of a novel 3D human cartilage model system to investigate changes in cartilage associated with osteoarthritis. PhD Thesis, Cardiff University.
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Abstract

Osteoarthritis (OA) is the most prevalent form of degenerative joint diseases and affects about 13% of the world’s population with patients over 65 years of age reflecting the largest group of patients (Matthews and Hunter 2011). OA is characterized by a progressive degeneration of joint cartilage and results in impaired function of affected joints, pain and negatively affects quality of life of patients. Several biomarkers for the detection of early OA were already described (Mobasheri 2013), but none of them is reliable and quantifiable.Therefore, a need for novel biomarkers for OA exists to improve diagnosis when overt changes in cartilage are not yet detectable.The aim of my thesis was to identify novel biomarkers for OA which can be used for early diagnosis. I focused on changes in the glycosylation of proteoglycans, especially on chondroitin sulphate (CS) glycosaminoglycan (GAG) chains. Using human chondrocyte progenitor cells, a novel 3D cartilage model was developed and characterized. The resulting cartilage constructs showed similar biochemical, histological and mechanical properties like native articular cartilage. To investigate the effects of inflammatory cytokines, which are also present in OA, on changes in expression of glycosylation-related genes, treated and untreated constructs were analyzed using microarrays.Analysis showed that although genes for GAG chain synthesis were downregulated,the sulphotransferase GalNAc4S-6ST was significantly upregulated. This enzyme catalyzes the formation of GalNAc4,6diS, which has high biological activity (Mikami and Kitagawa 2013). In addition, the expression of serglycin was strongly increased after inflammatory stimulation. These results show that novel epitopes containing GalNAc4,6diS or serglycin could be potential biomarkers for OA. Besides the experiments with cartilage constructs, analysis of the CS chain of decorin isolated from human skin fibroblasts showed that inflammatory stimulation alters the length and composition of CS chains.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Dentistry
Subjects: Q Science > Q Science (General)
Uncontrolled Keywords: Cartilage, Osteoarthritis, Tissue Engineering, Biomarker, Extracellular Matrix, Inflammation Cartilage, Osteoarthritis, Tissue Engineering, Biomarker, Extracellular Matrix, Inflammation
Funders: Arthritis Research UK, President's Scholarship
Date of First Compliant Deposit: 30 March 2016
Last Modified: 22 Apr 2018 01:30
URI: http://orca-mwe.cf.ac.uk/id/eprint/72433

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