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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/10.1002/jcb.10442" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/jcb.10442</a>
Pages
941–953
Issue
5
Volume
88
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
Coordinate down-regulation of cartilage matrix gene expression in Bcl-2 deficient chondrocytes is associated with decreased SOX9 expression and decreased mRNA stability.
Publisher
An entity responsible for making the resource available
Journal of cellular biochemistry
Date
A point or period of time associated with an event in the lifecycle of the resource
2003
2003-04
Subject
The topic of the resource
Aggrecans; Animals; C-Type; Cell Line; Chondrocytes/*physiology; Collagen Type II/genetics/metabolism; Dactinomycin; Down-Regulation; Extracellular Matrix Proteins/analysis/genetics/*metabolism; Gene Expression Regulation; Glycoproteins/analysis/genetics/*metabolism; High Mobility Group Proteins/genetics/*metabolism; Lectins; Matrilin Proteins; Messenger/analysis/biosynthesis; Polymerase Chain Reaction/methods; Proteoglycans/genetics/metabolism; Proto-Oncogene Proteins c-bcl-2/deficiency/genetics/*physiology; Rats; RNA; RNA Stability; Signal Transduction; SOX9 Transcription Factor; Transcription Factors/genetics/*metabolism; Transfection
Creator
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Kinkel Mary D; Horton Walter E Jr
Description
An account of the resource
The anti-apoptotic protein Bcl-2 has been shown to function in roles unrelated to apoptosis in a variety of cell types. We have previously reported that loss of Bcl-2 expression alters chondrocyte morphology and modulates aggrecan expression via an apoptosis-independent pathway. Here we show that Bcl-2 is required for chondrocytes to maintain expression of a variety of cartilage-specific matrix proteins. Using quantitative, real-time PCR, we demonstrate that Bcl-2-deficient chondrocytes coordinately down-regulate genes coding for hyaline cartilage matrix proteins including collagen II, collagen IX, aggrecan, and link protein. The decrease in steady-state level of these mRNA transcripts results, in part, from decreased mRNA stability in Bcl-2-deficient chondrocytes. Transcriptional regulation is also likely involved because chondrocytes with decreased Bcl-2 levels show decreased expression of SOX9, a transcription factor necessary for expressing the major cartilage matrix proteins. In contrast, chondrocytes constitutively expressing Bcl-2 have a stable phenotype when subjected to loss of serum factor signaling. These cells maintain high levels of SOX9, as well as the SOX9 targets collagen II and aggrecan. These results suggest that Bcl-2 is involved in a pathway important for maintaining a stable chondrocyte phenotype.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1002/jcb.10442" target="_blank" rel="noreferrer noopener">10.1002/jcb.10442</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2003
Aggrecans
Animals
C-Type
Cell Line
Chondrocytes/*physiology
Collagen Type II/genetics/metabolism
Dactinomycin
Down-Regulation
Extracellular Matrix Proteins/analysis/genetics/*metabolism
Gene Expression Regulation
Glycoproteins/analysis/genetics/*metabolism
High Mobility Group Proteins/genetics/*metabolism
Horton Walter E Jr
Journal of cellular biochemistry
Kinkel Mary D
Lectins
Matrilin Proteins
Messenger/analysis/biosynthesis
Polymerase Chain Reaction/methods
Proteoglycans/genetics/metabolism
Proto-Oncogene Proteins c-bcl-2/deficiency/genetics/*physiology
Rats
RNA
RNA Stability
Signal Transduction
SOX9 Transcription Factor
Transcription Factors/genetics/*metabolism
Transfection
-
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
An entity responsible for making the resource available
Arthritis & Rheumatology
Date
A point or period of time associated with an event in the lifecycle of the resource
2019
2019-04
Subject
The topic of the resource
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
An unambiguous reference to the resource within a given context
<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