Effects of rhein on human articular chondrocytes in alginate beads.
This study was designed to investigate the effects of rhein, the active metabolite of diacerhein, on the metabolic functions of human chondrocytes cultured in alginate beads. Enzymatically isolated osteoarthritic (OA) chondrocytes were cultured in alginate beads in a well-defined culture medium for 12 days. Rhein was tested in a range of concentrations comprised between 10(-7) and 4 x 10(-5)M, in the presence or absence of 10(-10)M IL-1beta. Interleukin (IL)-6 and -8, macrophage inflammatory protein (MIP-1beta), stromelysin-1 (MMP-3), aggrecan (AGG), tissue inhibitor of metalloproteinases-1 (TIMP-1), prostaglandin E(2) (PGE(2)) and nitric oxide (NO) productions were assayed. Cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) mRNA steady-state levels were also quantified. In the basal condition, 10(-5)M rhein increased by 46.5% the production of AGG, decreased by 17-30% the production of IL-6, MMP-3, NO and MIP-1beta but enhanced by 50% the production of PGE(2). IL-1beta increased IL-6, IL-8, MIP-1beta, NO, PGE(2) and MMP-3 productions, but inhibited AGG and TIMP-1 synthesis. Rhein partially reversed the effect of IL-1beta on TIMP-1 and NO production, had no effect on AGG, IL-6 and MIP-1beta production, but up-regulated the IL-1beta stimulated PGE(2) production. The COX-2 and iNOS mRNA levels and IL-8 production were not modified by rhein.Overall, these results contribute to explain the clinical efficiency of rhein and give new information on its mechanisms of action.
Sanchez
Christelle
C
Bone and Cartilage Metabolism Research Unit, Institute of Pathology, CHU Sart-Tilman, 4000 Liège, Belgium.
Mathy-Hartert
Marianne
M
Deberg
Michelle A
MA
Ficheux
Herve
H
Reginster
Jean Yves L
JY
Henrotin
Yves E
YE
D053674:Aggrecans; D000880:Anthraquinones / Q000494:pharmacology*; D054407:Chemokine CCL4; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D037181:Lectins, C-Type; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D053674:Aggrecans; D000880:Anthraquinones; D054407:Chemokine CCL4; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D037181:Lectins, C-Type; D019402:Macrophage Inflammatory Proteins; D011509:Proteoglycans; D019715:Tissue Inhibitor of Metalloproteinase-1; D009569:Nitric Oxide; D004247:DNA; D006899:Mixed Function Oxygenases; D007770:L-Lactate Dehydrogenase; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone; C020491:rhein