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J. Biol. Chem., Vol. 276, Issue 40, 36983-36992, October 5, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/40/36983    most recent M011442200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Demoor-Fossard, M. Articles by Rédini, F. Search for Related Content PubMed PubMed Citation Articles by Demoor-Fossard, M. Articles by Rédini, F.

A Composite Element Binding the Vitamin D Receptor and the Retinoic X Receptor  Mediates the Transforming Growth Factor- Inhibition of Decorin Gene Expression in Articular Chondrocytes^*

Magali Demoor-Fossard, Philippe Galéra, Manoranjan Santra^§, Renato V. Iozzo^§¶, Jean-Pierre Pujol, and Françoise Rédini

From the  Laboratoire de Biochimie du Tissu Conjonctif, Faculté de Médecine, niv. 3, 14032 Caen cedex, France and the ^§ Department of Pathology, Anatomy, and Cell Biology and ^¶ Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Decorin, a small leucine-rich proteoglycan may play an important role in the attempt of cartilage repair initiated by chondrocytes in early stages of osteoarthritis, through its ability to bind collagen fibrils and growth factors such as transforming growth factor- (TGF-). We previously demonstrated that TGF- decreased decorin mRNA steady state levels in articular chondrocytes (Demoor, M., Rédini, F., Boittin, M., and Pujol, J.-P. (1998) Biochim. Biophys. Acta 1398, 179-191). Here, we investigated the effect of TGF- on decorin gene expression in both primary cultures of articular chondrocytes and chondrocytes dedifferentiated by serial passages. Transient transfection of cells with plasmid constructs of the decorin promoter linked to the luciferase reporter gene revealed transcriptional repression by TGF-, in fully differentiated as well as dedifferentiated chondrocytes. Experiments with 5'-deleted constructs allowed characterization of a TGF--responsive element in the shortest construct (base pairs (bp) 155/+269). DNase I footprinting analysis delineated a negative TGF--responsive region between 140 and 111 bp in the decorin proximal promoter. Gel retardation assays demonstrated that TGF- modulates decorin gene expression through transcription factors, the nature and mode of action of which depend on the differentiation state of the chondrocytes; two DNA-protein complexes were formed in the region 144/127 bp with nuclear extracts from primary chondrocytes, whereas a higher mobility complex was observed in the 127/111 bp region for dedifferentiated cells. Antibodies against vitamin D and retinoic acid receptors used in supershift experiments showed that these nuclear receptors are involved in the regulation of decorin gene expression in articular chondrocytes.

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