当前位置： SCI文献检索 > OSTEOARTHRITIS AND CARTILAGE期刊下所有文献 > Stimulating effect of diacerein on TGF-beta1 and beta2 expression in articular chondrocytes cultured with and without interleukin-1.

Stimulating effect of diacerein on TGF-beta1 and beta2 expression in articular chondrocytes cultured with and without interleukin-1.

Abstract：

OBJECTIVE:Diacetylrhein or diacerein has shown efficacy in the treatment of both major forms of osteoarthritis (OA), coxarthrosis as well as gonarthrosis, improving clinical symptoms of the disease (pain reduction and algo-functional index). Both in-vitro and animal models studies suggest that diacerein may have also disease-modifying effects. The drug exerts inhibitory effects on interleukin-1-induced expression of cartilage degrading enzymes. However, its mechanism of action is not completely understood. In view of the role that could play the transforming growth factor (TGF)-beta system in the repair potentialities of OA cartilage, we studied the effect of diacerein on the expression of TGF-beta isoforms 1, 2 and 3 and that of their receptor types I and II in cultured bovine chondrocytes. METHODS:Cultured bovine articular chondrocytes were treated with 10(-5) m diacerein, 10 ng/ml IL-1beta or the combination diacerein+interleukin (IL)-1, and the expression of both TGF-beta isoforms 1, 2 and 3 and that of their receptors TbetaR-I and TbetaR-II was determined by Northern-blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Cell transfections of cDNA constructs containing sequences of the 5'-upstream region of TGF-beta1 promoter were also performed to determine their transcriptional activity in diacerein-treated cultures. RESULTS:The data indicated that diacerein enhances the expression of TGF-beta1 and TGF-beta2. This effect was also found in the presence of IL-1, albeit with smaller intensity. In contrast, the levels of TGF-beta3 and receptors I and II remained unaffected or slighty modified by the compound. Treatment of cells transiently transfected with TGF-beta1 promoter constructs suggested that the stimulating effect on TGF-beta1 expression is mediated by the region -1038 to -1132 base pars. CONCLUSION:The results suggest that diacerein effects on matrix synthesis and turn-over previously reported in cultured articular chondrocytes might be explained in part by the ability of the drug to enhance TGF-beta1 and TGF-beta2 expression in these cells. This mechanism of action may account for the potential disease-modifying properties of diacerein and might give clues as to how future anti-osteoarthritic drugs should be designed.

journal_name

Osteoarthritis Cartilage

journal_title

Osteoarthritis and cartilage

authors

Felisaz N,Boumediene K,Ghayor C,Herrouin JF,Bogdanowicz P,Galerra P,Pujol JP

doi

10.1053/joca.1998.0199

keywords:

subject

Has Abstract

pub_date

1999-05-01 00:00:00

pages

255-64

issue

eissn

1063-4584

issn

1522-9653

pii

S1063-4584(98)90199-6

journal_volume

pub_type

杂志文章

在线工具

Stimulating effect of diacerein on TGF-beta1 and beta2 expression in articular chondrocytes cultured with and without interleukin-1.