Titre : | Up-regulation of type II collagen gene by 17 beta-estradiol in articular chondrocytes involves Sp1/3, Sox-9, and estrogen receptor alpha (2014) |
Auteurs : | L. Maneix ; A. Servent ; B. Poree ; D. Ollitrault ; T. Branly ; N. Bigot ; N. Boujrad ; G. Flouriot ; M. Demoor ; K. Boumediene ; S. Moslemi ; P. Galera |
Type de document : | Article : texte imprimé |
Dans : | J MOL MED (92, 2014-08-02) |
Article en page(s) : | p.1179-1200 |
Langues: | Anglais |
Mots-clés : |
Mots-clés cheval OESTROGENE ; OSTEOARTHRITEEquivoc Cartilage ; Médecine Humaine |
Résumé : | The existence of a link between estrogen deprivation and osteoarthritis (OA) in postmenopausal women suggests that 17?-estradiol (17?-E2) may be a modulator of cartilage homeostasis. Here, we demonstrate that 17?-E2 stimulates, via its receptor human estrogen receptor ? 66 (hER?66), type II collagen expression in differentiated and dedifferentiated (reflecting the OA phenotype) articular chondrocytes. Transactivation of type II collagen gene (COL2A1) by ligand-independent transactivation domain (AF-1) of hER?66 was mediated by \223GC\224 binding sites of the ?266/ ?63-bp promoter, through physical interactions between ER?, Sp1/Sp3, Sox9, and p300, as demonstrated in chromatin immunoprecipitation (ChIP) and Re-Chromatin Immuno- Precipi tation (Re-ChIP) assays in primary and dedifferentiated cells. 17?-E2 and hER?66 increased the DNA-binding activities of Sp1/Sp3 and Sox-9 to both COL2A1 promoter and enhancer regions. Besides, Sp1, Sp3, and Sox-9 small interfering RNAs (siRNAs) prevented hER?66-induced transactivation of COL2A1, suggesting that these factors and their respective cis-regions are required for hER?66-mediated COL2A1 up-regulation. Our results highlight the genomic pathway by which 17?-E2 and hER?66 modulate Sp1/Sp3 heteromer binding activity and simultaneously participate in the recruitment of the essential factors Sox-9 and p300 involved respectively in the chondrocyte-differentiated status and COL2A1 transcriptional activation. These novel findings could therefore be attractive for tissue engineering of cartilage in OA, by the fact that 17?- E2 could promote chondrocyte redifferentiation. |
Cote du document numérique : | 17356 |
Classement cheval : | A17 |