Item Details

title

The redox regulation of alpha 5 beta 1 integrin stimulated MMP production in articular chondrocytes

author

Erickson, Elizabeth Alice

abstract

Elevated levels of reactive oxygen species (ROS) have been observed in the cartilage of osteoarthritis (OA) patients and may contribute to the degradation of the articular cartilage extracellular matrix (ECM). ROS have been shown to serve as secondary messengers in integrin and cytokine signaling pathways which stimulate chondrocyte production of ECM-degrading enzymes called matrix metalloproteinases (MMPs). Fibronectin fragment (FN-f) stimulation of the &alpha5&beta1 integrin increases intracellular levels of ROS in chondrocytes, while antioxidants block FN-f stimulated MMP-13 expression, demonstrating ROS are critical regulators of this pathway. However, the means by which ROS regulate this pathway are unknown. Therefore, the objective of this work was to investigate the source of ROS and the mechanism by which ROS mediate the FN-f stimulation of MMP production.

subject

MAP kinases

matrix metalloproteinases

osteoarthritis

reactive oxygen species

redox signaling

sulfenic acid

contributor

Loeser, Richard F (committee chair)

Hantgan, Roy R (committee member)

McPhail, Linda C (committee member)

Poole, Leslie B (committee member)

Furdui, Cristina M (committee member)

date

2012-01-18T09:35:28Z (accessioned)

2011 (issued)

degree

Molecular Medicine and Translational Science (discipline)

embargo

forever (terms)

10000-01-01 (liftdate)

identifier

http://hdl.handle.net/10339/36425 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation