4 research outputs found
Foregut caustic injuries: results of the world society of emergency surgery consensus conference
Rhein, the metabolite of diacerhein, reduces the proliferation of osteoarthritic chondrocytes and synoviocytes without inducing apoptosis
International audienceObjective: The aim of this study was to determine the effects of pharmacologically relevant concentrations of rhein (1,8âdihydroxyâ3âcarboxyanthraquinone) on the cell proliferation rate of human chondrocytes and synoviocytes.Methods: Cultures of human osteoarthritic synoviocytes and chondrocytes were incubated with 10â6, 10â5, and 10â4â
M rhein. [3H]thymidine incorporation was used to determine rhein proliferative effects after incubation periods of 24â
h, 48â
h, and 1 week. The cytotoxicity of the drug was assayed with a nonradioactive assay kit. Nuclear extracts were used to detect variations in cellâcycle proteins (p21, p27, and cyclin D1) by Western blotting. The effect of rhein on apoptosis was investigated by measurement of caspaseâ3/7 activity and DNA fragmentation.Results: Rhein was found to downregulate the proliferation rate of both chondrocytes and synoviocytes, twoâfold for 10â5â
M rhein and fiveâ to sixâfold for 10â4â
M rhein. No cytotoxicity of the drug was observed. Rhein (10â4â
M) decreased caspaseâ3/7 activity and did not induce DNA fragmentation. Western blots showed that 10â4â
M rhein increased the expression of p21 and/or p27, but not that of cyclin D1.Conclusions: Rhein has previously been shown to reduce the interleukin (IL)â1ÎČ deleterious effects on osteoarthritis (OA) cartilage through inhibition of the expression of degrading enzymes. Here, rhein was also found to inhibit proliferation of both synoviocytes and chondrocytes, suggesting that the drug may decrease the development of the inflammatory synovial tissue that accompanies joint pathologies. Both its antiâcatabolic and antiâproliferative effects may explain its beneficial effect in the treatment of joint diseases