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Text
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<a href="http://doi.org/10.1002/art.40751" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/art.40751</a>
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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
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Genetic inactivation of ZCCHC6 suppresses IL-6 expression and reduces the severity of experimental osteoarthritis in mice.
Publisher
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Arthritis & rheumatology (Hoboken, N.J.)
Date
A point or period of time associated with an event in the lifecycle of the resource
2018
2018-10
Creator
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Ansari Mohammad Y; Khan Nazir M; Ahmad Nashrah; Green Jonathan; Novak Kimberly; Haqqi Tariq M
Description
An account of the resource
OBJECTIVE: Cytokine expression is tightly regulated post-transcriptionally but high levels of IL-6 in osteoarthritis (OA) indicate disruption of regulatory mechanisms. ZCCHC6 enzyme is implicated in post-transcriptional regulation of inflammatory cytokine expression but its role in OA pathogenesis is unknown. Here we studied whether ZCCHC6 directs the expression of IL-6 and influence OA pathogenesis in vivo. METHODS: Human and mouse chondrocytes were stimulated with recombinant IL-1beta. We knocked down the expression of ZCCHC6 in human chondrocytes by siRNAs. IL-6 transcript stability was determined by Actinomycin-D chase and 3'-uridylation of miRNAs was determined by deep sequencing. Zcchc6-/- mice were produced by gene targeting. OA was surgically induced in the knee joints of mice and the disease severity was scored using a semi-quantitative scoring system. RESULTS: ZCCHC6 was markedly upregulated in the damaged cartilage from human OA patients and from wild type mice with surgically-induced OA. Overexpression of ZCCHC6 induced the expression of IL-6 and its knockdown reduced the IL-6 transcript stability and IL-1beta-induced expression in chondrocytes. Reintroduction of Zcchc6 in Zcchc6-/- chondrocytes rescued the IL-1beta-induced
Identifier
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<a href="http://doi.org/10.1002/art.40751" target="_blank" rel="noreferrer noopener">10.1002/art.40751</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).
2018
Ahmad Nashrah
Ansari Mohammad Y
Arthritis & rheumatology (Hoboken, N.J.)
Department of Anatomy & Neurobiology
Green Jonathan
Haqqi Tariq M
Khan Nazir M
NEOMED College of Medicine
Novak Kimberly
-
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/10.1002/art.40751" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/art.40751</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).
Pages
583-593
Issue
4
Volume
71
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
Genetic Inactivation of ZCCHC6 Suppresses Interleukin‐6 Expression and Reduces the Severity of Experimental Osteoarthritis in Mice.
Publisher
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Arthritis & Rheumatology
Date
A point or period of time associated with an event in the lifecycle of the resource
2019
2019-04
Subject
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ANIMAL experimentation; CARTILAGE; CARTILAGE cells; DACTINOMYCIN; DNA-binding proteins; GENE expression; GENETIC aspects; IN vivo studies; INTERLEUKINS; MICE; MICRORNA; OSTEOARTHRITIS; PREVENTION; SEQUENCE analysis; SEVERITY of illness index; SYNOVITIS; TRANSCRIPTION factors
Creator
An entity primarily responsible for making the resource
Ansari Mohammad Y; Khan Nazir M; Ahmad Nashrah; Green Jonathan; Novak Kimberly; Haqqi Tariq M
Description
An account of the resource
Objective: Cytokine expression is tightly regulated posttranscriptionally, but high levels of interleukin‐6 (IL‐6) in patients with osteoarthritis (OA) indicate that regulatory mechanisms are disrupted in this disorder. The enzyme ZCCHC6 (zinc‐finger CCHC domain–containing protein 6; TUT‐7) has been implicated in posttranscriptional regulation of inflammatory cytokine expression, but its role in OA pathogenesis is unknown. The present study was undertaken to investigate whether ZCCHC6 directs the expression of IL‐6 and influences OA pathogenesis in vivo. Methods: Human and mouse chondrocytes were stimulated with recombinant IL‐1β. Expression of ZCCHC6 in human chondrocytes was knocked down using small interfering RNAs. IL‐6 transcript stability was determined by actinomycin D chase, and 3′‐uridylation of microRNAs was determined by deep sequencing. Zcchc6−/− mice were produced by gene targeting. OA was surgically induced in the knee joints of mice, and disease severity was scored using a semiquantitative grading system. Results: ZCCHC6 was markedly up‐regulated in damaged cartilage from human OA patients and from wild‐type mice with surgically induced OA. Overexpression of ZCCHC6 induced the expression of IL‐6, and its knockdown reduced IL‐6 transcript stability and IL‐1β–induced IL‐6 expression in chondrocytes. Reintroduction of Zcchc6 in Zcchc6−/− mouse chondrocytes rescued the IL‐1β–induced IL‐6 expression. Knockdown of ZCCHC6 reduced the population of micro‐RNA 26b (miR‐26b) with 3′‐uridylation by 60%. Zcchc6−/− mice with surgically induced OA produced low levels of IL‐6 and exhibited reduced cartilage damage and synovitis in the joints. Conclusion: These findings indicate that ZCCHC6 enhances IL‐6 expression in chondrocytes through transcript stabilization and by uridylating miR‐26b, which abrogates repression of IL‐6. Inhibition of IL‐6 expression and significantly reduced OA severity in Zcchc6−/− mice identify ZCCHC6 as a novel therapeutic target to inhibit disease pathogenesis. [ABSTRACT FROM AUTHOR]
Identifier
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<a href="http://doi.org/10.1002/art.40751" target="_blank" rel="noreferrer noopener">10.1002/art.40751</a>
2019
Ahmad Nashrah
ANIMAL experimentation
Ansari Mohammad Y
Arthritis & Rheumatology
Cartilage
CARTILAGE cells
Dactinomycin
Department of Anatomy & Neurobiology
DNA-Binding Proteins
Gene Expression
GENETIC aspects
Green Jonathan
Haqqi Tariq M
In Vivo Studies
Interleukins
June 2019 Update
Khan Nazir M
Mice
MicroRNA
NEOMED College of Medicine
Novak Kimberly
Osteoarthritis
Prevention
Sequence Analysis
Severity of Illness Index
SYNOVITIS
Transcription Factors