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40
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Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1242/jcs.247353" target="_blank" rel="noreferrer noopener">http://doi.org/10.1242/jcs.247353</a>
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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).
ISSN
1477-9137 0021-9533
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Locate full-text within NEOMED Library's e-journal collections
<a href="http://neomed.idm.oclc.org/login?url=http://doi.org/10.1242/jcs.247353" target="_blank" rel="noreferrer noopener">NEOMED Full-text Holding (if available) - Proxy DOI: 10.1242/jcs.247353</a>
<p>Users with a NEOMED Library login can search for full-text journal articles at the following url: <a href="https://libraryguides.neomed.edu/home">https://libraryguides.neomed.edu/home</a></p>
Update Year & Number
October 2020 List
NEOMED College
NEOMED College of Medicine
NEOMED Department
Department of Anatomy & Neurobiology
NEOMED Student Publications
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Mitochondrial dysfunction triggers catabolic response in chondrocytes via ROS mediated activation of JNK/AP1 pathway.
Publisher
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Journal of Cell Science
Date
A point or period of time associated with an event in the lifecycle of the resource
2020
2020-10-23
Subject
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Inflammation; Osteoarthritis; Chondrocytes; Redox; cFos-AP1; JNK
Creator
An entity primarily responsible for making the resource
Ansari M Y;Ahmad N;Voleti S;Wase SJ;Novak K;Haqqi TM
Description
An account of the resource
Mitochondrial function is impaired in osteoarthritis (OA) but its impact on cartilage catabolism is not fully understood. Here, we investigated the molecular mechanism of mitochondrial dysfunction-induced activation of catabolic response in chondrocytes. Using cartilage slices from normal and OA cartilage, we show that mitochondrial membrane potential was lower in OA cartilage which was associated with increased production of mitochondrial superoxide and catabolic genes (IL-6, COX-2, MMP-3,-9,-13 and ADAMTS5). Pharmacological induction of mitochondrial dysfunction in chondrocytes and cartilage explants using CCCP increased the mitochondrial superoxide production and the expression of IL-6, COX-2, MMP-3,-9-13 and ADAMTS5 and cartilage matrix degradation. Mitochondrial dysfunction induced expression of catabolic genes was dependent on JNK/AP1 pathway but not the NFκB pathway. Scavenging of mitochondrial superoxide with MitoTEMPO or pharmacological inhibition of JNK or cFos/cJun blocked the mitochondrial dysfunction-induced expression of the catabolic genes in chondrocytes. We demonstrate here that mitochondrial dysfunction contributes to OA pathogenesis via JNK/AP1 mediated expression of catabolic genes. Our data shows that AP1 could be used as a therapeutic target for OA management.
Identifier
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<a href="http://doi.org/10.1242/jcs.247353" target="_blank" rel="noreferrer noopener">10.1242/jcs.247353</a>
Format
The file format, physical medium, or dimensions of the resource
journalArticle
2020
Ahmad N
Ansari M Y
cFos-AP1
Chondrocytes
Department of Anatomy & Neurobiology
Haqqi TM
Inflammation
JNK
Journal of Cell Science
journalArticle
NEOMED College of Medicine
NEOMED Student Publications
Novak K
October 2020 List
Osteoarthritis
Redox
Voleti S
Wase SJ
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1016/j.joca.2020.08.014" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.joca.2020.08.014</a>
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
ISSN
1522-9653 1063-4584
Search for Full-text
Locate full-text within NEOMED Library's e-journal collections
<a href="http://neomed.idm.oclc.org/login?url=http://doi.org/10.1016/j.joca.2020.08.014" target="_blank" rel="noreferrer noopener">NEOMED Full-text Holding (if available) - Proxy DOI: 10.1016/j.joca.2020.08.014</a>
<p>Users with a NEOMED Library login can search for full-text journal articles at the following url: <a href="https://libraryguides.neomed.edu/home">https://libraryguides.neomed.edu/home</a></p>
Update Year & Number
October 2020 List
NEOMED College
NEOMED College of Medicine
NEOMED Department
Department of Anatomy & Neurobiology
NEOMED Student Publications
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Lysosomal dysfunction in osteoarthritis and aged cartilage triggers apoptosis in chondrocytes through BAX mediated release of cytochrome c.
Publisher
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Osteoarthritis and Cartilage
Date
A point or period of time associated with an event in the lifecycle of the resource
2020
2020-11-05
Subject
The topic of the resource
Osteoarthritis; Mitochondrial dysfunction; Apoptosis; Ageing; BAX; Lysosomal dysfunction
Creator
An entity primarily responsible for making the resource
Ansari M Y;Ball HC;Wase SJ;Novak K;Haqqi TM
Description
An account of the resource
OBJECTIVE: Lysosomes are the major catabolic organelle of the cell and regulate the macromolecular and organelle turnover and programmed cell death. Here, we investigated the lysosome dysfunction in cartilage and its role in chondrocytes apoptosis and the associated mechanism. DESIGN: Lysosomal acidification in OA and aged cartilage was determined by LysoSensor staining. Lysosomal function in chondrocytes was blocked by siRNA mediated depletion of LAMP2 or with lysosome inhibitors. Chondrocyte apoptosis was determined by LDH release, Caspase-3/7 activation, TUNEL and PI uptake assays. Loss of mitochondrial membrane potential (MMP/ΔΨM) and mitochondrial superoxide level was determined by JC-1 and MitoSOX staining, respectively. Colocalization of mitochondria with BAX and Cytochrome c was determined by immunostaining. DMM was performed to induce OA in mice. RESULTS: Lysosomal acidification was found to be significantly decreased in aged mouse and human and mouse OA cartilage which also showed increased chondrocyte apoptosis. Inhibition of lysosomal function resulted in increased oxidative stress, accumulation of dysfunctional mitochondria and apoptosis in chondrocytes in monolayer and in cartilage explant cultures. Depletion of LAMP2 expression or treatment of chondrocytes with lysosomal function inhibitors increased the expression and mitochondrial translocation of BAX leading to Cytochrome c release. Lysosomal dysfunction-induced apoptosis in chondrocytes was not blocked by antioxidants MitoTempo or DPI but was abrogated by inhibiting BAX. CONCLUSION: Lysosomal dysfunction induce apoptosis in chondrocytes through BAX-mediated mitochondrial damage and release of Cytochrome c. Our data points to lysosomal function restoration and/or BAX inhibition in chondrocytes as a therapeutic approach for OA.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1016/j.joca.2020.08.014" target="_blank" rel="noreferrer noopener">10.1016/j.joca.2020.08.014</a>
Format
The file format, physical medium, or dimensions of the resource
journalArticle
2020
ageing
Ansari M Y
Apoptosis
Ball HC
Bax
Department of Anatomy & Neurobiology
Haqqi TM
journalArticle
Lysosomal dysfunction
Mitochondrial dysfunction
NEOMED College of Medicine
NEOMED Student Publications
Novak K
October 2020 List
Osteoarthritis
Osteoarthritis and cartilage
Wase SJ