JAK/STAT but not @entity30511 / @entity30512 pathway mediates interleukin (IL)-6/soluble IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes. Association with a down-regulation of XXXX expression.

@entity291 @entity17837 @entity10512 @entity34121 @entity48105 @entity2924 @entity30511 @entity30512 @entity48434 @entity2720 @entity4286 @entity58077 @entity67552
Signal transducers and activators of transcription (STAT) factors are cytoplasmic proteins that can be activated by Janus kinases (JAK) and that modulate gene expression in response to cytokine receptor stimulation. STAT proteins dimerize, translocate into the nucleus, and activate specific target genes. In the present study, we show for the first time that @entity48105 (IL), in the presence of its soluble receptor (sIL-6R), induces activation of @entity67552 , @entity58077 , and @entity2924 / @entity34121 proteins in @entity291 articular chondrocytes. Western blotting and mobility shift assays demonstrated that this effect is accompanied by the DNA binding of the STAT proteins. The mitogen-activated protein kinase pathway was also activated in response to @entity17837 /sIL-6R association, as reflected by phosphorylation of @entity30511 and @entity30512 proteins. In these conditions, the expression of cartilage-specific matrix genes, type II collagen, aggrecan core, and link proteins was found to be markedly down-regulated. This negative effect was abolished by addition of @entity10512 , an inhibitor of the STAT activation, whereas blockade of the MAP kinases with @entity4286 was without significant effect. Thus, activation of the STAT signaling pathways, but not ERK-dependent pathways, is essential for down-regulation of the major cartilage-specific matrix genes by @entity17837 . In addition, a parallel reduction of @entity48434 expression, a key factor of chondrocyte phenotype, was found in these experimental conditions. These @entity17837 effects might contribute to the phenotype loss of chondrocytes in @entity2720 and the alteration of articular cartilage associated with this pathology.
