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Permanent link (DOI): https://doi.org/10.7939/R3S66B

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Collagen I: an aberrantly expressed molecule in chondrocytes or a key player in tissue stabilization and repair both in vivo and in vitro? Open Access

Descriptions

Other title
Subject/Keyword
Repair
Fibrocartilage
Collagen I
Hypoxia
Chondrocyte
Osteoarthritis
Dedifferentiation
Cartilage
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Barley, Randall Douglas Corwyn
Supervisor and department
Dr. Keith M. Bagnall, Department of Anatomy, United Arab Emirates University
Dr. Nadr M. Jomha, Department of Surgery, University of Alberta
Examining committee member and department
Dr. John Cinats, Department of Surgery, University of Alberta
Dr. Andrew J. Simmonds, Department of Cell Biology, University of Alberta
Mr. James Raso, Department of Surgery, University of Alberta
Dr. Kevin A. Hildebrand, Department of Surgery, University of Calgary
Department
Department of Surgery
Specialization

Date accepted
2010-02-03T21:47:52Z
Graduation date
2010-06
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Extrinsic repair techniques for the treatment of acute chondral injuries continue to yield suboptimal repair. The inability of these techniques to produce hyaline cartilage underscores the limitations in our understanding of basic chondrocyte biology. Conversely, intrinsic repair tissue has not been extensively studied despite the fact that it can yield hyaline-like cartilage and is commonly observed in osteoarthritis. Attempts at extrinsic repair could therefore benefit from a better understanding of the successes and failures inherent in the intrinsic repair process. Chondrocyte culture has typically been conducted under non-physiologic conditions whereby chondrocytes readily dedifferentiate. Consequently, much of the knowledge gained about chondrocytes has been misleading thus hindering advancements in chondrocyte biology and attempts at extrinsic articular cartilage (AC) repair. Hypoxic culture conditions, which are beneficial towards the preservation of the chondrocyte phenotype, remain insufficient due to elevated collagen I gene expression. As such, an appropriate model system does not yet exist in which to study physiologically-relevant chondrocyte biology. The presence and prevalence of collagen I in both degenerate and de novo osteoartritic tissue was examined immunohistochemically. Collagen I deposition during osteoarthritic progression was compared against IHC staining for collagen II and aggrecan. A novel model system was also evaluated for chondrocytic phenotype retention. To this end, hypoxic, high-density-monolayer-chondrocyte (HDMC) cultures were compared to freshly isolated chondrocytes for their ability to maintain a chondrocytic extracellular matrix (ECM) gene expression profile. HDMC culture conditions prevented the severe loss of the phenotype typically associated with conventional monolayer culture. Moreover, prolonged HDMC culture resulted in the formation of a complex ECM and a marked suppression of collagen I expression. This study also demonstrated that collagen I deposition occurs in osteoarthritic AC at the onset of structural damage and increases in response to increasing structural damage. Collagen I deposition was also found in different types of de novo cartilage associated with osteoarthritic joints and suggests that it plays an important role in intrinsic cartilage repair. Taken together, this work demonstrates that collagen I is a common feature in the ECM of structurally immature and structurally damaged AC and hence may play a role in tissue stabilization.
Language
English
DOI
doi:10.7939/R3S66B
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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