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- W2009314818 abstract "Abstract Objective To evaluate the expression and function of the orphan nuclear receptor Rev‐ErbAα in articular cartilage and to investigate its role in osteoarthritis (OA). Methods Expression of Rev‐ErbAα was analyzed at both the messenger RNA and protein levels in human and bovine articular cartilage and chondrocytes by real‐time polymerase chain reaction (TaqMan) and immunocytochemical techniques. The effects of cartilage catabolic and anabolic agents on the expression of Rev‐ErbAα were evaluated by TaqMan analysis. Overexpression was achieved by either adenoviral transduction or treatment with a peroxisome proliferator–activated receptor α agonist, whereas expression was suppressed by antisense oligonucleotides. Results Among the 48 known nuclear receptors, Rev‐ErbAα was found to be the most highly expressed in OA cartilage. It is known to function as a transcription repressor. Treatment of articular chondrocytes with known catabolic agents resulted in the induction of Rev‐ErbAα, whereas stimulation with anabolic agents led to a decrease in expression. Overexpression of the nuclear receptor was associated with an increase in the expression of matrix‐degrading enzymes such as matrix metalloproteinase 13 and aggrecanase. In contrast, a decrease in Rev‐ErbAα expression led to a concomitant reduction in the activity of matrix‐degrading enzymes. Conclusion This study is the first to demonstrate that Rev‐ErbAα is highly expressed in OA articular chondrocytes and that its expression is modulated by known cartilage catabolic and anabolic stimuli. We also demonstrated that modulation of Rev‐ErbAα expression in chondrocytes may be a novel means of regulating the expression and production of multiple matrix‐degrading enzymes. These observations suggest that Rev‐ErbAα may be a novel therapeutic target for OA." @default.
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- W2009314818 date "2006-10-30" @default.
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- W2009314818 title "Functional characterization of an orphan nuclear receptor, Rev-ErbAα, in chondrocytes and its potential role in osteoarthritis" @default.
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- W2009314818 doi "https://doi.org/10.1002/art.22170" @default.
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