Mechanisms and functional implications of aggrecan catabolism in cartilage and meniscal fibrocartilage (Book, 2007) [WorldCat.org]
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Mechanisms and functional implications of aggrecan catabolism in cartilage and meniscal fibrocartilage

Author: Christopher Garrison Wilson
Publisher: 2007.
Dissertation: Ph. D. Biomedical Engineering, Georgia Institute of Technology 2007
Edition/Format:   Thesis/dissertation : Document : Thesis/dissertation : State or province government publication : eBook   Computer File : English
Summary:
Arthritis includes many conditions of the joints characterized by inflammation, pain, and loss of joint function that affect 66 million people in the U.S. alone. During arthritic degeneration, chondrocytes exhibit downregulated synthesis of extracellular matrix molecules and upregulation of proteolytic enzymes. Fibrochondrocytes, found in meniscal fibrocartilage, appear to behave in a similar way.  Read more...
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Genre/Form: Academic theses
Material Type: Document, Thesis/dissertation, Government publication, State or province government publication, Internet resource
Document Type: Internet Resource, Computer File
All Authors / Contributors: Christopher Garrison Wilson
OCLC Number: 144635125
Notes: Temenoff, Johnna, Committee Member ; Levenston, Marc, Committee Chair ; Sandy, John, Committee Member ; Garca̕, Andrš, Committee Member ; Bellamkonda, Ravi, Committee Member.
Responsibility: by Christopher Garrison Wilson.
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Abstract:

Arthritis includes many conditions of the joints characterized by inflammation, pain, and loss of joint function that affect 66 million people in the U.S. alone. During arthritic degeneration, chondrocytes exhibit downregulated synthesis of extracellular matrix molecules and upregulation of proteolytic enzymes. Fibrochondrocytes, found in meniscal fibrocartilage, appear to behave in a similar way. Metalloproteinases, including matrix metalloproteinases (MMP) and a disintegrin and metollproteinase with thrombospondin motif (ADAMTS) class enzymes have demonstrated efficient, distinct aggrecan degradation in models of arthritis. ADAMTS-4 and ADAMTS-5 are thought to be primary mediators of pathologic aggrecan catabolism, while MMP-17 may be involved in ADAMTS activation. There is also growing evidence of metalloproteinase-independent mechanisms in aggrecan catabolism. The cysteine endopeptidase m-calpain has been detected in cartilage from arthritic joints, and chondrocytes can secrete this protease. The overall objective of this work was to investigate metalloproteinases and m-calpain as comediators of aggrecan turnover in articular cartilage and meniscal fibrocartilage. The central hypothesis was that metalloproteinases cooperate with m-calpain to mediate cytokine-induced aggrecan turnover and associated changes in tissue mechanics. Experiments involved using inhibitors to perturb protease systems, antibodies targeting aggrecan "neoepitopes" to characterize enzyme activity, and established methods of evaluating tissue compressive and shear properties. Models of degradation and de novo tissue assembly were used to investigate tissue-specific differences in aggrecan turnover. The results of this work demonstrate tissue-specific differences in the abundance and structure of aggrecan, and indicate that the mechanisms and extent of aggrecan processing in the meniscus is dependent on location within the tissue. The relationships between aggrecan structure and tissue material properties are discussed, along with implications for development, disease, and repair.

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