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Text
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URL Address
<a href="http://doi.org/10.1002/jcb.23025" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/jcb.23025</a>
Pages
1118–1129
Issue
4
Volume
112
Dublin Core
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Title
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The presence of extracellular matrix alters the chondrocyte response to endoplasmic reticulum stress.
Publisher
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Journal of cellular biochemistry
Date
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2011
2011-04
Subject
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*Stress; Animals; Apoptosis/drug effects; Articular/cytology; Blotting; Cartilage; Cattle; Cells; Chondrocytes/cytology/drug effects/*metabolism; Cultured; DNA-Binding Proteins/genetics/metabolism; Dose-Response Relationship; Drug; Endoplasmic Reticulum/*metabolism; Extracellular Matrix/*metabolism; Glucose/pharmacology; Heat-Shock Proteins/genetics/metabolism; Physiological; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Thapsigargin/pharmacology; Time Factors; Transcription Factors/genetics/metabolism; Tunicamycin/pharmacology; Western
Creator
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Nugent Ashleigh E; McBurney Denise L; Horton Walter E Jr
Description
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The objective of this study was to test the hypothesis that extracellular matrix (ECM) would alter the endoplasmic reticulum (ER) stress response of chondrocytes. Chondrocytes were isolated from calf knees and maintained in monolayer culture or suspended in collagen I to form spot cultures (SCs). Our laboratory has shown that bovine chondrocytes form cartilage with properties similar to native cartilage after 2-4 weeks in SCs. Monolayer cultures treated with ER stressors glucose withdrawal (-Glu), tunicamycin (TN), or thapsigargin (TG) up-regulated Grp78 and Gadd153, demonstrating a complete ER stress response. SCs were grown at specific times from 1 day to 6 weeks before treatment with ER stressors. Additionally, SCs grown for 1, 2, or 6 weeks were treated with increasing concentrations of TN or TG. Western blotting of SCs for Grp78 indicated that increased ECM accumulation results in delayed expression; however, Grp78 mRNA is up-regulated in response to ER stressors even after 6 weeks in culture. SCs treated with ER stressors did not up-regulate Gadd153, suggesting that the cells experienced ER stress but would not undergo apoptosis. In fact, SCs undergo apoptosis upon ER stress treatment after 0-1 day of growth; however, after 4 days and to 6 weeks, apoptosis in treated samples was not different than controls. Pro-survival molecules Bcl-2 and Bag-1 were up-regulated upon ER stress in SCs. These results suggest that presence of ECM confers protection from ER stressors. Future studies involving chondrocyte physiology should focus on responses in conditions more closely mimicking the in vivo cartilage environment.
Identifier
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<a href="http://doi.org/10.1002/jcb.23025" target="_blank" rel="noreferrer noopener">10.1002/jcb.23025</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Stress
2011
Animals
Apoptosis/drug effects
Articular/cytology
Blotting
Cartilage
Cattle
Cells
Chondrocytes/cytology/drug effects/*metabolism
Cultured
Department of Anatomy & Neurobiology
DNA-Binding Proteins/genetics/metabolism
Dose-Response Relationship
Drug
Endoplasmic Reticulum/*metabolism
Extracellular Matrix/*metabolism
Glucose/pharmacology
Heat-Shock Proteins/genetics/metabolism
Horton Walter E Jr
Journal of cellular biochemistry
McBurney Denise L
NEOMED College of Medicine
Nugent Ashleigh E
Physiological
Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
Reverse Transcriptase Polymerase Chain Reaction
Thapsigargin/pharmacology
Time Factors
Transcription Factors/genetics/metabolism
Tunicamycin/pharmacology
Western